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Widespread recognition of 5' splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides.
Genes Dev. 2012 May 15; 26(10):1098-109.GD

Abstract

An established paradigm in pre-mRNA splicing is the recognition of the 5' splice site (5'ss) by canonical base-pairing to the 5' end of U1 small nuclear RNA (snRNA). We recently reported that a small subset of 5'ss base-pair to U1 in an alternate register that is shifted by 1 nucleotide. Using genetic suppression experiments in human cells, we now demonstrate that many other 5'ss are recognized via noncanonical base-pairing registers involving bulged nucleotides on either the 5'ss or U1 RNA strand, which we term "bulge registers." By combining experimental evidence with transcriptome-wide free-energy calculations of 5'ss/U1 base-pairing, we estimate that 10,248 5'ss (∼5% of human 5'ss) in 6577 genes use bulge registers. Several of these 5'ss occur in genes with mutations causing genetic diseases and are often associated with alternative splicing. These results call for a redefinition of an essential element for gene expression that incorporates these registers, with important implications for the molecular classification of splicing mutations and for alternative splicing.

Authors+Show Affiliations

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22588721

Citation

Roca, Xavier, et al. "Widespread Recognition of 5' Splice Sites By Noncanonical Base-pairing to U1 snRNA Involving Bulged Nucleotides." Genes & Development, vol. 26, no. 10, 2012, pp. 1098-109.
Roca X, Akerman M, Gaus H, et al. Widespread recognition of 5' splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides. Genes Dev. 2012;26(10):1098-109.
Roca, X., Akerman, M., Gaus, H., Berdeja, A., Bennett, C. F., & Krainer, A. R. (2012). Widespread recognition of 5' splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides. Genes & Development, 26(10), 1098-109. https://doi.org/10.1101/gad.190173.112
Roca X, et al. Widespread Recognition of 5' Splice Sites By Noncanonical Base-pairing to U1 snRNA Involving Bulged Nucleotides. Genes Dev. 2012 May 15;26(10):1098-109. PubMed PMID: 22588721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Widespread recognition of 5' splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides. AU - Roca,Xavier, AU - Akerman,Martin, AU - Gaus,Hans, AU - Berdeja,Andrés, AU - Bennett,C Frank, AU - Krainer,Adrian R, PY - 2012/5/17/entrez PY - 2012/5/17/pubmed PY - 2012/8/4/medline SP - 1098 EP - 109 JF - Genes & development JO - Genes Dev. VL - 26 IS - 10 N2 - An established paradigm in pre-mRNA splicing is the recognition of the 5' splice site (5'ss) by canonical base-pairing to the 5' end of U1 small nuclear RNA (snRNA). We recently reported that a small subset of 5'ss base-pair to U1 in an alternate register that is shifted by 1 nucleotide. Using genetic suppression experiments in human cells, we now demonstrate that many other 5'ss are recognized via noncanonical base-pairing registers involving bulged nucleotides on either the 5'ss or U1 RNA strand, which we term "bulge registers." By combining experimental evidence with transcriptome-wide free-energy calculations of 5'ss/U1 base-pairing, we estimate that 10,248 5'ss (∼5% of human 5'ss) in 6577 genes use bulge registers. Several of these 5'ss occur in genes with mutations causing genetic diseases and are often associated with alternative splicing. These results call for a redefinition of an essential element for gene expression that incorporates these registers, with important implications for the molecular classification of splicing mutations and for alternative splicing. SN - 1549-5477 UR - https://www.unboundmedicine.com/medline/citation/22588721/Widespread_recognition_of_5'_splice_sites_by_noncanonical_base_pairing_to_U1_snRNA_involving_bulged_nucleotides_ L2 - http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=22588721 DB - PRIME DP - Unbound Medicine ER -