From the Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, Massachusetts 01003
One of the exciting frontiers in the field of
RNA editing is the phenomenon of RNA-guided nucleotide modification. In
this type of editing, a nucleotide in a precursor RNA is converted to
another form by an RNA-protein complex
(RNP)1 (1). The RNPs that
mediate these reactions include a guide RNA that provides site
specificity through base pairing with the substrate and a set of
proteins, one of which catalyzes the modification reaction. The
phenomenon was first discovered in the modification of ribosomal RNA
(rRNA) in the nucleolus of eukaryotic cells (Fig. 1). Two common alterations are relevant,
formation of 2'-O-methylated nucleosides (Nm; the guided
mechanism was reported in 1996) and conversion of uridine to
pseudouridine (
INTRODUCTION
TOP
INTRODUCTION
Occurrence and Effects of...
Guided Nm and
New Types of Guide...
Archaeal rRNA and tRNA...
Perspective
REFERENCES
; the guided process was reported in 1997) (2-4).
These modifications are mediated by two large, heterogeneous
populations of RNPs that are modification type-specific and
site-specific. The RNPs contain a small nucleolar RNA (snoRNA) and
several associated proteins, and the snoRNA-protein complexes are
called snoRNPs ("snorps"). The snoRNA provides the guide function,
and an integral snoRNP protein catalyzes the modification reaction.
When discovered, this type of reaction scheme was not only novel but in
sharp contrast to the rRNA modification schemes used by Eubacteria,
where the synthesis of Nm and
is mediated (thus far) by protein
enzymes that do not include an RNA co-factor (5). Guided modification
was subsequently discovered to apply to the U6 snRNA (small nuclear RNA
in vertebrates and Caenorhabditis elegans) and likely to
mRNA (mammals, trypanosomes) (6-9). Strikingly, from an
evolutionary perspective, the new paradigm was also discovered (in
2000) to apply to Archaeal organisms where substrates include tRNA as
well as rRNA (10).
View larger version (47K):
[in a new window]
Fig. 1.
Modification of rRNA by snoRNPs.
A, overview of ribosome biogenesis. The scheme shown is
generic; see Ref. 15 for additional details. Modifying snoRNPs act on
pre-rRNA in the nucleolus during or after transcription. The
dashed boxes identify snoRNP substructures
depicted in panels B and C. B,
interaction of a box C/D guide snoRNA with its rRNA substrate. The
diagram lists the four core snoRNP proteins (yeast names) and
identifies nucleotides in the C and D elements predicted to be in
contact with Snu13p. Nop1p (fibrillarin) is the putative
methyltransferase. C, interaction of a box H/ACA guide
snoRNA with its substrate. Cbf5p (dyskerin) is the putative synthase.
Recent advances have revealed guided modification to be more complex
and widespread and are almost certainly a harbinger of exciting new
developments to come. Key developments include: 1) identification of
new guide RNAs that reside in mammalian Cajal bodies (these RNAs are
specific for the four snRNAs transcribed by RNA polymerase II (pol II),
which are thought to undergo maturation and possibly RNP assembly at
this location (11)); 2) evidence that the trypanosome trans-spliced
leader is a substrate for guided modification (9); and 3) successful
development of the first cell-free Nm modification system, using
recombinant archaeal components (12). Taken together, these findings
argue that additional modifying RNPs and substrates subjected to
RNA-guided modification will be discovered. In this minireview we
describe the present state of knowledge about the various RNP-modifying
complexes, the processes they mediate, where in the cell these
reactions occur, and the range of substrates. Because of limited space
the reader is also referred to other recent reviews (1, 13-18).
![]() |
Occurrence and Effects of Nm and ![]() |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The Nm and nucleotides appear to be universal among rRNAs and
small stable RNAs such as splicing snRNAs, tRNAs, and snoRNAs; however,
the abundance and locations of these nucleotides vary phylogenetically
(19-21). Although the modifications are believed to be beneficial,
evidence is still sparse. Blocking Nm or
modification at a global
level in yeast rRNA has strong negative effects on growth rate (22,
23), and the absence of Nm and
in U2 snRNA impairs its assembly
into an active spliceosome in Xenopus oocytes (24). New
three-dimensional modification maps of rRNA show the modifications are
heavily concentrated in regions of the ribosome known or predicted to
be functionally important, suggesting that the modifications benefit
ribosome activity, either directly or indirectly (25-27). At the level
of individual modifications blocking Nm or
synthesis in bacterial
or yeast rRNA has, thus far, resulted in either no detectable effect or
only a slight effect on growth rate, implying that many (perhaps most)
modifications affect ribosome structure and function in a synergistic
way (25, 27, 28). The changes in RNA structure caused by modification
could "fine-tune" many events in rRNA folding, rRNP assembly, or
ribosome activity as well as trafficking and half-life. The same
reasoning applies to modification of the small RNAs (e.g.
Ref. 29).
![]() |
Guided Nm and ![]() |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Since their discovery, scores of guide snoRNAs have been
identified for rRNA, primarily in yeast and human cells, and it seems likely that most Nm and modifications in cytoplasmic rRNA are formed by snoRNPs (1). In support of this view, candidate guide snoRNAs
have been identified in yeast for 51 of 55 known Nm sites and 30 of 44
s (30, 31).2 However, it
is possible that some modifications are created by enzymes without an
RNA cofactor. The snoRNPs are thought to act early in rRNA synthesis as
the modification level of uncleaved, primary transcripts is high (14,
15, 32-34). This situation is consistent with modification occurring
co-transcriptionally or in large pre-ribosome complexes that evolve
into the individual subunits (15) (Fig. 1A). In addition to
mediating modification reactions, a few snoRNPs are required for
processing (cleavage) of pre-rRNA (17). The corresponding snoRNAs
interact directly with rRNA, but the actual functions of the snoRNPs in
processing are not known in most cases. Additional roles for snoRNAs
also seem possible. For example, in the context of guided modification, a snoRNP could affect other aspects of RNA synthesis or function in
addition to modification (see below).
Each general class of guide snoRNAs and snoRNPs is both modification type-specific and site-specific (Fig. 1, B and C). Each class of snoRNA contains one or two targeting motifs that act independently at sites in the same or different pre-rRNA(s), and each class of snoRNP contains a different set of four common core proteins. During modification, the guide sequence selects (by complementary base pairing) a target sequence in the substrate RNA, and modification occurs within this target sequence at a characteristic distance from a short "box" element in the interacting snoRNA.
The Nm guide snoRNAs contain one or two pairs of small, distinguishing sequence elements called boxes C and D, and C' and D'. These elements define the C/D family of snoRNAs, which also includes a few species involved in rRNA processing (16, 17). Boxes C/D occur near the 5' and 3' ends of the RNA and boxes C'/D' are located internally. The methylation guide sequence is located upstream of the box D/D' element and consists of 10-21 nucleotides (1, 35).
The canonical C/D boxes are required for snoRNA stability and proper end formation (note that vertebrate snoRNAs are typically derived from introns of protein genes (16)). Remarkably, the C/D elements are also necessary and sufficient for localizing snoRNAs to the nucleolus, which occurs by way of the Cajal bodies in vertebrate cells and in at least some cases functionally related nucleolar bodies in yeast (11, 18, 36) (see below). These last findings indicate that snoRNA synthesis and localization are coupled (16).
The methylating snoRNPs have four common core proteins. The total number of proteins in a particle is not known nor is it known if all modifying snoRNPs are identical except for the RNA component. The core proteins in yeast (and humans) are: Snu13p (15.5 kDa), Nop56p (hNop56p), Nop58p (hNop58p), and Nop1p (fibrillarin). Snu13p binds to a characteristic stem-asymmetric loop-stem structure that includes the canonical C/D elements in the loop portion (Fig. 1B). Interestingly, Snu13p is also part of the U4 snRNP where it binds a similar, common RNA fold called the K-turn (37, 38). Nop56p and Nop58p are related to each other and both interact with snoRNA (16, 39).
Nop1p (fibrillarin) is generally accepted to be the 2'-O-methyltransferase. In support of this contention, point mutations in methylase-like elements have been shown to block ribose methylation globally in yeast cells. In addition, a crystal structure of an archaeal ortholog that contains the methylase signature elements showed that most of the protein has a three-dimensional structure like that of many known S-adenosylmethionine-dependent methylases (40). In a process yet to be defined but assuredly interesting, the snoRNP methylase acts on a ribose of a nucleotide that is initially base paired with the snoRNA guide sequence. The target site is 5 nucleotides upstream of box D/D', located 4-5 nucleotides within the region of complementarity (Fig. 1B). Key mechanistic questions to be resolved include whether base pairing actually occurs over the full length of the guide sequence (9 base pairs are required for methylation to occur (41)) and if accessibility to the target nucleotide involves the action of other snoRNP or non-snoRNP proteins such as a helicase. Each type of box element is required for methylation: boxes D and D' because they are spatial determinants and the C/D and C'/D' pairs because they affect protein binding (1, 37, 39).
The guide snoRNAs have characteristic small sequence elements
referred to as boxes H and ACA and are members of a larger family of
H/ACA snoRNAs (1, 27, 42) (Fig. 1C). Like the C/D elements,
the H and ACA boxes and neighboring duplexes are required for
processing of snoRNA precursors, protein binding, and localization (16,
18). Most H/ACA snoRNAs are guide RNAs. However, as with the C/D snoRNA
family, a few participate in rRNA processing, and one, telomerase RNA
(from mammals but not yeast), guides telomere formation (17, 18). The
snoRNAs that guide
formation have a bi-partite, consensus secondary
structure consisting of 5'-duplex-hinge-duplex-tail-3' domains. The H
and ACA boxes occur in the single-stranded hinge and 3' tail segments,
respectively. Substrate targeting involves base pairing through two
short guide sequences in a loop portion of the duplex structures and a
distance measurement of ~14-15 nucleotides from the H or ACA box (3, 4). Substrate binding places the uridine to be isomerized in a pocket
between the flanking paired regions.
The four core proteins of the H/ACA snoRNPs differ from those in the
C/D snoRNPs, and the same uncertainties exist about the numbers and
types of proteins among the individual snoRNPs. The core proteins in
yeast (and human) include: Cbf5p (dyskerin), Gar1p (hGar1p), Nhp2p
(hNhp2p), and Nop10p (hNop10p). Cbf5p is accepted to be the
pseudouridine synthase. In support of this view, Cbf5p and orthologs
contain elements conserved among known synthases, and point
mutations in two such elements in yeast Cbf5p disrupt
formation in
rRNA in a global manner (23). Natural mutations in human dyskerin have
been linked to a premature aging disease in humans (dyskeratosis
congenita), but interference with telomerase function may be the basis
of the disease rather than defective
synthesis (17). Interestingly,
the Nhp2p protein in the H/ACA snoRNPs and the Snu13p protein in the
C/D snoRNPs are related to each other (in yeast, 38% identity and 61%
similarity), suggesting the proteins have related functions. The
bi-partite nature of the H/ACA snoRNAs is reflected in electron
micrograph images of two yeast snoRNPs, where two oblong lobes are
joined at one end to form a V-like structure estimated at 15 nm long and 12 nm wide (43). In the context of a growing ribosome, these snoRNPs are roughly 10% the mass of the ribosome, which would favor
their acting before a compact preribosomal RNP is formed (Fig.
1A).
Results from recent structure studies of a bacterial synthase
provide valuable insight into how this type of modifying enzyme interacts with its substrate (44). The results should apply to guided
formation too, as the bacterial enzyme, Escherichia coli
TruB, and Cbf5p are homologs, and Cbf5p has the motifs that occur in
the active site region of TruB. The crystal structure of a TruB enzyme
complexed with a tRNA fragment reveals that the enzyme causes the
target uracil to flip out and the folded tRNA structure to be
destabilized. These distortions could provide access for a conserved
aspartate to attack and initiate the reaction in which the glycosidic
bond is broken and the uracil base is rotated and reattached (44,
45).
![]() |
New Types of Guide RNAs, Cellular Locations, and Substrates in Eukaryotes |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In a surprising development, new candidate human guide RNAs
have been discovered to reside exclusively in Cajal (coiled) bodies (11, 46). The small Cajal body-specific RNAs, called scaRNAs, have
the hallmark features of the archetypical snoRNAs, except that some
have an unusual arrangement and content of guide motifs. Among the
current set of scaRNAs are: species with both Nm and modification motifs and species that resemble the classically defined
guide snoRNAs. Guide sequences have been identified thus far in the
scaRNAs for known modifications in pol II-transcribed snRNAs (U1, U2,
U4, and U5).
Newly synthesized snoRNAs that participate in modification (and processing) of pre-rRNA are also known to localize to Cajal bodies before entering the nucleolar complex (11, 47-49). These results suggest that the nucleolar specific guide RNAs (and possibly additional RNAs) might also undergo modification in Cajal bodies (CBs). The new dichotomy in localization of snoRNA-like guide RNAs indicates diversity in the determinants responsible for retaining RNA in the Cajal bodies. Selection could involve substrate binding or interaction with CB proteins that are specific for the nascent scaRNPs.
Adding to the excitement, new results with yeast have identified novel
structures called nucleolar bodies (NBs), which have overlapping
functions with Cajal bodies (36, 50) (Fig.
2). Newly synthesized U3 and U14 snoRNAs,
and C/D and H/ACA snoRNP proteins have been detected in the NBs. Strong
evidence that both snoRNAs and snRNAs undergo maturation events in
nucleolar bodies comes from the discovery that an enzyme, Tgs1p, that
hypermethylates the 5'-cap structures of a subset of snoRNAs and the
pol II snRNAs appears to be localized to this structure (51).
Consistent with parallel functions of CBs and NBs, the vertebrate
ortholog of Tgs1p occurs in the Cajal bodies, suggesting that cap
formation of snoRNAs takes place in this nuclear compartment (50).
(Note that most vertebrate snoRNAs undergo 5'-end processing and lack caps.) The parallel is not complete, however, as hypermethylation of
pol II snRNAs is known to occur in the cytoplasm and Tgs1 protein localizes to the cytoplasm as well as the CBs (50).
|
It seems possible that a variety of mRNAs might be substrates for guided modification, based on two fascinating recent reports. In the first, an analysis of mouse and human brain small RNAs identified a candidate Nm snoRNA with a guide sequence that is complementary (18 nt) to mRNA for a serotonin receptor (8). The mRNA transcripts undergo alternative splicing and adenosine to inosine editing at four sites to yield proteins with different signal transduction potentials. Guided methylation is predicted to occur at one of the editing sites, all of which are close to each other (within a 13-nt span) and proximal to an alternative splice site (10 nt from the closest editing site). Clearly, modification at such an editing site could have several important effects on subsequent expression and function of the protein products. Intriguingly, this putative guide RNA and several others are encoded at imprinted gene loci, suggesting they may have a role in imprinting (8, 52).
Also striking are results arguing that a trypanosome spliced leader (SL
RNA) undergoes guided modification (9). Here, a candidate guide RNA
was identified (in both the nucleolus and nucleoplasm) that is
predicted to target a site known to undergo modification, and mutating
the region of complementarity in the SL RNA blocked this modification.
Because the SL RNA is spliced to all mRNAs, a single modification
could affect the synthesis and activity of many proteins. These two
situations with mRNAs raise the specter that RNA-guided
modification may play important roles in altering the structure and
function of mRNAs (and proteins) as well as stable RNAs.
![]() |
Archaeal rRNA and tRNA Are Also Modified by snoRNP-like Complexes |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The Archaeal kingdom contains orthologous components of the
eukaryotic Nm and snoRNPs (10). Scores of candidate Nm guide RNAs
for rRNA and tRNA have been identified, and recently, the first
putative
guide RNAs have also been reported (four RNA species)
(53). Although in vivo verification of guide function is not
yet possible, modifications are known to occur at many predicted Nm
sites in rRNA and tRNA and at six predicted
sites in rRNA. The
snoRNA-like guide RNAs are called sRNAs and the modifying complexes are sRNPs.
Relative to the eukaryotic counterparts, the archaeal machinery is
somewhat simpler. Although the Nm guide sRNAs can also have one or two
targeting motifs, the sizes are generally at the lower end of the
eukaryotic size range and they have shorter guide elements. Three
candidate sRNAs identified thus far are unusually short and contain
only one of the two targeting domains of the archetypical guide
snoRNAs; these RNAs closely resemble
guide RNAs in Trypanosomes
(9), which are early branching eukaryotes. Provocatively, a candidate
Nm guide RNA has been discovered in an intron of an archaeal pre-tRNA
that is specific for two sites methylated in the same tRNA; this
arrangement suggests that RNA-guided modification may be able to act in
cis (10, 54). As for the proteins, the set of C/D core proteins is
simpler too, with three proteins rather than four. Accounting for this
latter difference, archaeal C/D sRNPs contain a single ortholog of the
eukaryotic Nop56p and Nop58p proteins (aNop56). Like its eukaryotic
counterpart, the archaeal variant of Snu13p/15.5 kDa, ribosomal protein
aL7a, is a dual purpose protein, which binds to kink turns in both rRNA and sRNA (55). All four orthologs of the eukaryotic
snoRNP proteins
have been identified in the archaea (56).
In a particularly important breakthrough, RNA-guided methylation has
been demonstrated in vitro, with a simple, reconstituted archaeal sRNP and a short rRNA fragment as substrate (12). Accurate, site-specific methylation of the rRNA fragment was achieved with an
sRNP complex formed by incubating a cognate sRNA (expressed in
vitro) with the three C/D core proteins. This demonstration shows
that an sRNP complex containing only the core proteins and guide RNA is
sufficient to catalyze site-specific methylation; the results also
strengthen the belief that Nop1p is the Nm methylase. This advance
should spur attempts to establish homologous eukaryotic systems and
in vitro systems for modification.
![]() |
Perspective |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
It is reasonable to expect that the list of RNAs subjected to
RNA-guided modification will increase, in particular for eukaryotic nascent RNAs that move through the Cajal bodies or nucleolus. In
addition to U1, U2, U4, and U5 snRNAs, Cajal bodies also contain U11
and U12 splicing snRNAs and U7 snRNA (involved in 3'-end formation of
histone mRNA). Similarly, the growing number of RNAs that appear to
have a nucleolar phase is also growing and now includes the U6 snRNA,
tRNA, RNase P RNA, signal recognition particle RNA, telomerase RNA,
mRNA, and perhaps HIV transcripts (57, 58). Moreover, the many new,
small non-coding RNAs discovered recently are also candidates for
guided modifications (59). The results of the recent past suggest that
the field of RNA-guided modification will remain an exciting frontier
of the RNA world for many years.
![]() |
FOOTNOTES |
---|
* This minireview will be reprinted in the 2003 Minireview Compendium, which will be available in January, 2004. This work was supported by National Institutes of Health Grant GM19351.
To whom correspondence should be addressed: Dept. of Biochemistry
and Molecular Biology, Lederle Graduate Research Tower, University of
Massachusetts, Amherst, MA 01003. Tel.: 413-545-0353; Fax:
413-545-3291; E-mail: 4nier@biochem.umass.edu.
Published, JBC Papers in Press, November 12, 2002, DOI 10.1074/jbc.R200023200
2 W. A. Decatur and M. J. Fournier, unpublished data.
![]() |
ABBREVIATIONS |
---|
The abbreviations used are:
RNP, ribonucleoprotein;
rRNA, ribosomal RNA;
Nm, ribose-methylated
nucleotide;
, pseudouridine;
snoRNA, small nucleolar RNA;
snoRNP, small nucleolar ribonucleoprotein complex;
snRNA, small nuclear RNA;
sRNA/sRNP, snoRNA-like RNA/RNP;
CB, Cajal body;
NB, nucleolar body;
scaRNA/RNP, small Cajal body RNA/RNP;
pol II, RNA polymerase II;
nt, nucleotide(s);
SL, spliced leader.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1. |
Kiss, T.
(2001)
EMBO J.
20,
3617-3622 |
2. | Kiss-Laszlo, Z., Henry, Y., Bachellerie, J. P., Caizergues-Ferrer, M., and Kiss, T. (1996) Cell 85, 1077-1088[Medline] [Order article via Infotrieve] |
3. | Ni, J., Tien, A. L., and Fournier, M. J. (1997) Cell 89, 565-573[Medline] [Order article via Infotrieve] |
4. | Ganot, P., Bortolin, M. L., and Kiss, T. (1997) Cell 89, 799-809[Medline] [Order article via Infotrieve] |
5. | Ofengand, J., and Rudd, K. (2000) in The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions (Garrett, R. A. , Douthwaite, S. R. , Liljas, A. , Matheson, A. T. , Moore, P. B. , and Noller, H. F., eds) , pp. 175-189, ASM Press, Washington, D. C. |
6. | Tycowski, K. T., You, Z. H., Graham, P. J., and Steitz, J. A. (1998) Mol. Cell 2, 629-638[Medline] [Order article via Infotrieve] |
7. |
Ganot, P.,
Jady, B. E.,
Bortolin, M. L.,
Darzacq, X.,
and Kiss, T.
(1999)
Mol. Cell. Biol.
19,
6906-6917 |
8. |
Cavaille, J.,
Buiting, K.,
Kiefmann, M.,
Lalande, M.,
Brannan, C. I.,
Horsthemke, B.,
Bachellerie, J. P.,
Brosius, J.,
and Huttenhofer, A.
(2000)
Proc. Natl. Acad. Sci. U. S. A.
97,
14311-14316 |
9. |
Liang, X. H., Xu, Y. X.,
and Michaeli, S.
(2002)
RNA
8,
237-246 |
10. | Dennis, P. P., Omer, A., and Lowe, T. (2001) Mol. Microbiol. 40, 509-519[CrossRef][Medline] [Order article via Infotrieve] |
11. |
Darzacq, X.,
Jady, B. E.,
Verheggen, C.,
Kiss, A. M.,
Bertrand, E.,
and Kiss, T.
(2002)
EMBO J.
21,
2746-2756 |
12. |
Omer, A. D.,
Ziesche, S.,
Ebhardt, H.,
and Dennis, P. P.
(2002)
Proc. Natl. Acad. Sci. U. S. A.
99,
5289-5294 |
13. | Weinstein, L. B., and Steitz, J. A. (1999) Curr. Opin. Cell Biol. 11, 378-384[CrossRef][Medline] [Order article via Infotrieve] |
14. | Warner, J. R. (2001) Cell 107, 133-136[Medline] [Order article via Infotrieve] |
15. | Fatica, A., and Tollervey, D. (2002) Curr. Opin. Cell Biol. 14, 313-318[CrossRef][Medline] [Order article via Infotrieve] |
16. | Filipowicz, W., and Pogacic, V. (2002) Curr. Opin. Cell Biol. 14, 319-327[CrossRef][Medline] [Order article via Infotrieve] |
17. | Kiss, T. (2002) Cell 109, 145-148[Medline] [Order article via Infotrieve] |
18. | Terns, M. P., and Terns, R. M. (2002) Gene Expr. 10, 17-39[Medline] [Order article via Infotrieve] |
19. | Grosjean, H., and Benne, R. (eds) (1998) Modification and Editing of RNA , ASM Press, Washington, D. C. |
20. |
Gu, J.,
Chen, Y.,
and Reddy, R.
(1998)
Nucleic Acids Res.
26,
160-162 |
21. |
Rozenski, J.,
Crain, P. F.,
and McCloskey, J. A.
(1999)
Nucleic Acids Res.
27,
196-197 |
22. | Tollervey, D., Lehtonen, H., Jansen, R., Kern, H., and Hurt, E. C. (1993) Cell 72, 443-457[Medline] [Order article via Infotrieve] |
23. |
Zebarjadian, Y.,
King, T.,
Fournier, M. J.,
Clarke, L.,
and Carbon, J.
(1999)
Mol. Cell. Biol.
19,
7461-7472 |
24. |
Yu, Y. T.,
Shu, M. D.,
and Steitz, J. A.
(1998)
EMBO J.
17,
5783-5795 |
25. | Decatur, W. A., and Fournier, M. J. (2002) Trends Biochem. Sci. 27, 344-351[CrossRef][Medline] [Order article via Infotrieve] |
26. | Hansen, M. A., Kirpekar, F., Ritterbusch, W., and Vester, B. (2002) RNA (N. Y.) 8, 202-213 |
27. | Ofengand, J. (2002) FEBS Lett. 514, 17-25[CrossRef][Medline] [Order article via Infotrieve] |
28. | King, T. H., Liu, B., McCully, R. R., and Fournier, M. J. (2003) Mol. Cell, in press |
29. |
Newby, M. I.,
and Greenbaum, N. L.
(2001)
RNA
7,
833-845 |
30. |
Lowe, T. M.,
and Eddy, S. R.
(1999)
Science
283,
1168-1171 |
31. |
Samarsky, D. A.,
and Fournier, M. J.
(1999)
Nucleic Acids Res.
27,
161-164 |
32. | Udem, S. A., and Warner, J. R. (1972) J. Mol. Biol. 65, 227-242[Medline] [Order article via Infotrieve] |
33. | Salim, M., and Maden, B. E. (1973) Nature 244, 334-336[Medline] [Order article via Infotrieve] |
34. | Peculis, B. A. (2001) RNA (N. Y.) 7, 207-219 |
35. | Bachellerie, J. P., Michot, B., Nicoloso, M., Balakin, A., Ni, J., and Fournier, M. J. (1995) Trends Biochem. Sci. 20, 261-264[CrossRef][Medline] [Order article via Infotrieve] |
36. |
Verheggen, C.,
Mouaikel, J.,
Thiry, M.,
Blanchard, J. M.,
Tollervey, D.,
Bordonne, R.,
Lafontaine, D. L.,
and Bertrand, E.
(2001)
EMBO J.
20,
5480-5490 |
37. | Watkins, N. J., Segault, V., Charpentier, B., Nottrott, S., Fabrizio, P., Bachi, A., Wilm, M., Rosbash, M., Branlant, C., and Luhrmann, R. (2000) Cell 103, 457-466[Medline] [Order article via Infotrieve] |
38. |
Klein, D. J.,
Schmeing, T. M.,
Moore, P. B.,
and Steitz, T. A.
(2001)
EMBO J.
20,
4214-4221 |
39. |
Cahill, N. M.,
Friend, K.,
Speckmann, W., Li, Z. H.,
Terns, R. M.,
Terns, M. P.,
and Steitz, J. A.
(2002)
EMBO J.
21,
3816-3828 |
40. |
Wang, H.,
Boisvert, D.,
Kim, K. K.,
Kim, R.,
and Kim, S. H.
(2000)
EMBO J.
19,
317-323 |
41. |
Cavaille, J.,
and Bachellerie, J. P.
(1998)
Nucleic Acids Res.
26,
1576-1587 |
42. | Balakin, A. G., Smith, L., and Fournier, M. J. (1996) Cell 86, 823-834[Medline] [Order article via Infotrieve] |
43. | Watkins, N. J., Gottschalk, A., Neubauer, G., Kastner, B., Fabrizio, P., Mann, M., and Luhrmann, R. (1998) RNA (N. Y.) 4, 1549-1568 |
44. | Hoang, C., and Ferre-D'Amare, A. R. (2001) Cell 107, 929-939[Medline] [Order article via Infotrieve] |
45. |
Gu, X.,
Liu, Y.,
and Santi, D. V.
(1999)
Proc. Natl. Acad. Sci. U. S. A.
96,
14270-14275 |
46. |
Jady, B. E.,
and Kiss, T.
(2001)
EMBO J.
20,
541-551 |
47. |
Samarsky, D. A.,
Fournier, M. J.,
Singer, R. H.,
and Bertrand, E.
(1998)
EMBO J.
17,
3747-3757 |
48. |
Narayanan, A.,
Speckmann, W.,
Terns, R.,
and Terns, M. P.
(1999)
Mol. Biol. Cell
10,
2131-2147 |
49. | Lukowiak, A. A., Narayanan, A., Li, Z. H., Terns, R. M., and Terns, M. P. (2001) RNA (N. Y.) 7, 1833-1844 |
50. |
Verheggen, C.,
Lafontaine, D. L.,
Samarsky, D.,
Mouaikel, J.,
Blanchard, J. M.,
Bordonne, R.,
and Bertrand, E.
(2002)
EMBO J.
21,
2736-2745 |
51. | Mouaikel, J., Verheggen, C., Bertrand, E., Tazi, J., and Bordonne, R. (2002) Mol. Cell 9, 891-901[Medline] [Order article via Infotrieve] |
52. |
Cavaille, J.,
Seitz, H.,
Paulsen, M.,
Ferguson-Smith, A. C.,
and Bachellerie, J. P.
(2002)
Hum. Mol. Genet.
11,
1527-1538 |
53. |
Tang, T. H.,
Bachellerie, J. P.,
Rozhdestvensky, T.,
Bortolin, M. L.,
Huber, H.,
Drungowski, M.,
Elge, T.,
Brosius, J.,
and Huttenhofer, A.
(2002)
Proc. Natl. Acad. Sci. U. S. A.
99,
7536-7541 |
54. |
d'Orval, B. C.,
Bortolin, M. L.,
Gaspin, C.,
and Bachellerie, J. P.
(2001)
Nucleic Acids Res.
29,
4518-4529 |
55. |
Kuhn, J. F.,
Tran, E. J.,
and Maxwell, E. S.
(2002)
Nucleic Acids Res.
30,
931-941 |
56. |
Watanabe, Y.,
and Gray, M. W.
(2000)
Nucleic Acids Res.
28,
2342-2352 |
57. |
Pederson, T.
(1998)
Nucleic Acids Res.
26,
3871-3876 |
58. |
Michienzi, A.,
Cagnon, L.,
Bahner, I.,
and Rossi, J. J.
(2000)
Proc. Natl. Acad. Sci. U. S. A.
97,
8955-8960 |
59. |
Storz, G.
(2002)
Science
296,
1260-1263 |