Cited by 110RNA Research and SplicingRNA and protein synthesis mechanismsRNA regulation and disease

A stem/loop in U6 RNA defines a conformational switch required for pre-mRNA splicing.

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Fortner, D M, Troy, R G, Brow, D A·1994·Genes & Development

Abstract

U6 small nuclear RNA (snRNA) is an essential component of the spliceosome, the ribonucleoprotein complex that carries out the splicing of pre-mRNAs. The precise function of U6 RNA is unknown, but it has been proposed to participate directly in catalysis of the splicing reaction. We present biochemical and genetic evidence for an intramolecular stem/loop structure in the 3' half of U6 RNA of the yeast Saccharomyces cerevisiae that is mutually exclusive with the intermolecular base-pairing between U6 RNA and U4 snRNA. Strains with mutations that stabilize the U6 RNA 3'-intramolecular stem exhibit cold-sensitive growth and accumulate free U4 RNA, indicative of a block in U4/U6 snRNP assembly. The cold sensitivity can be partially suppressed by overexpression of U4 RNA. Mutations that disrupt base-pairing in the intramolecular 3' stem and mutations elsewhere in U6 RNA also suppress the growth defect. We conclude that a large conformational switch, involving melting of the U6 RNA 3' stem, is required for U4/U6 snRNP assembly. We hypothesize that formation of the U6 RNA intramolecular 3' stem after U4 RNA leaves the assembled spliceosome serves to activate U6 RNA for splicing by juxtaposing regions in U6 RNA that interact with U2 small nuclear RNA.

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Crossref · 10.1101/gad.8.2.221

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  • rs2807267 lies within an enhancer peak specific for T cells and is 948bps downstream of the RNA U6 small nuclear 320 pseudogene (RNU6-320P).

    “This variant lies within an enhancer peak specific for T cells and is 948bps downstream of the RNA U6 small nuclear 320 pseudogene (RNU6-320P), a component of the U6 small nuclear ribonucleoprotein (snRNP) that is part of the spliceosome and is responsible for the splicing of introns from pre-mRNA (14) (Fig. 2B).”

    From Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility (2019) · cites this paper as [14]

    The Abstract (page not provided) says U6 small nuclear RNA is an essential component of the spliceosome, which splices pre-mRNA. It does not identify RNU6-320P or establish that this pseudogene is a functional spliceosomal component. The variant’s enhancer and distance annotations are also not addressed in this paper. (LLM, conf=0.88)

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Research works printed but not linked: 3

  1. Rymond, B.C. and M. Rosbash. 1992. Yeast pre-mRNA splicing. The molecular and cellular biology of the yeast Saccharo- myces: Gene expression, (eds. E.W. Jones, J.R. Pringle, and J.R. Broach) pp. 143-192. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
  2. Treco, D.A. 1989. Saccharomyces cerevisiae, Current protocols in molecular biology (eds F.M. Ausubel, R. Brent, R.E. Kings- ton, D.D. Moore, J.G. Seidman, J.A. Smith, and K. Struhl), pp. 13.12.1-13.12.3. Greene Publishing Associates and Wiley-Interscience, New York.
  3. Zavanelli, M.I., J.S. Britton, A.H. Igel, and M. Ares, Jr. 1994. Mutations in an essential U2 snRNA structure cause cold sensitive U2 snRNP function by favoring competing alter- native U2 RNA structures. Mol. Cell. Biol, (in press).

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Authors
Fortner, D. M., Troy, R. G., & Brow, D. A.
Affiliations
University of Wisconsin System (US)
Venue
Genes & Development
Published
1994-01
Volume
8
Issue
2
Pages
221-233
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2104728352
Cited by
110
References
62
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 4 · 2013: 2 · 2012: 4
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Chicago Community Trust
  • Searle Scholars Program
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM 07215, T32GM007215)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
U6 small nuclear RNA, conformational switching, pre-mRNA splicing, spliceosome, U4 snRNA, U2 snRNA, Saccharomyces cerevisiae, RNA base pairing
MeSH terms
Base Sequence, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, Phenotype, RNA Splicing, RNA, Fungal, RNA, Messenger, RNA, Small Nuclear, Saccharomyces cerevisiae, Suppression, Genetic

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