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Interactions between the terminal bases of mammalian introns are retained in inosine-containing pre-mRNAs.
EMBO J. 1995 Jul 03; 14(13):3236-46.EJ

Abstract

Nuclear pre-mRNA splicing has a fundamentally similar two-step mechanism to that employed by group II self-splicing introns. It is believed that nuclear pre-mRNA splicing involves a network of RNA-RNA interactions which form the catalytic core of the active spliceosome. We show here a non-Watson-Crick interaction between the first and last guanosine residues of a mammalian intron. As in Saccharomyces cerevisiae, substitution of the conserved guanosines at the 5' and 3' splice sites by A and C respectively, specifically suppresses step 2 splicing defects resulting from the individual mutations. No other combination of terminal nucleotides was able to restore splicing. We additionally provide independent evidence for an indirect interaction between other nucleotides of the consensus splice sites during step 2 of splicing. Substitution of the nucleotide in the +3 position of the 5' splice site affects competition between closely spaced AG dinucleotides at the 3' splice site, although the interaction is not via direct differential base pairing. Finally, we show that complete substitution of guanosine residues by inosine in a pre-mRNA has only a modest effect upon step 2 of splicing, although earlier spliceosome assembly steps are impaired. Predictions can thus be made about the precise configuration of the non-Watson-Crick interaction between the terminal residues.

Authors+Show Affiliations

Department of Biochemistry, University of Cambridge, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7621835

Citation

Deirdre, A, et al. "Interactions Between the Terminal Bases of Mammalian Introns Are Retained in Inosine-containing Pre-mRNAs." The EMBO Journal, vol. 14, no. 13, 1995, pp. 3236-46.
Deirdre A, Scadden J, Smith CW. Interactions between the terminal bases of mammalian introns are retained in inosine-containing pre-mRNAs. EMBO J. 1995;14(13):3236-46.
Deirdre, A., Scadden, J., & Smith, C. W. (1995). Interactions between the terminal bases of mammalian introns are retained in inosine-containing pre-mRNAs. The EMBO Journal, 14(13), 3236-46.
Deirdre A, Scadden J, Smith CW. Interactions Between the Terminal Bases of Mammalian Introns Are Retained in Inosine-containing Pre-mRNAs. EMBO J. 1995 Jul 3;14(13):3236-46. PubMed PMID: 7621835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions between the terminal bases of mammalian introns are retained in inosine-containing pre-mRNAs. AU - Deirdre,A, AU - Scadden,J, AU - Smith,C W, PY - 1995/7/3/pubmed PY - 1995/7/3/medline PY - 1995/7/3/entrez SP - 3236 EP - 46 JF - The EMBO journal JO - EMBO J VL - 14 IS - 13 N2 - Nuclear pre-mRNA splicing has a fundamentally similar two-step mechanism to that employed by group II self-splicing introns. It is believed that nuclear pre-mRNA splicing involves a network of RNA-RNA interactions which form the catalytic core of the active spliceosome. We show here a non-Watson-Crick interaction between the first and last guanosine residues of a mammalian intron. As in Saccharomyces cerevisiae, substitution of the conserved guanosines at the 5' and 3' splice sites by A and C respectively, specifically suppresses step 2 splicing defects resulting from the individual mutations. No other combination of terminal nucleotides was able to restore splicing. We additionally provide independent evidence for an indirect interaction between other nucleotides of the consensus splice sites during step 2 of splicing. Substitution of the nucleotide in the +3 position of the 5' splice site affects competition between closely spaced AG dinucleotides at the 3' splice site, although the interaction is not via direct differential base pairing. Finally, we show that complete substitution of guanosine residues by inosine in a pre-mRNA has only a modest effect upon step 2 of splicing, although earlier spliceosome assembly steps are impaired. Predictions can thus be made about the precise configuration of the non-Watson-Crick interaction between the terminal residues. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/7621835/Interactions_between_the_terminal_bases_of_mammalian_introns_are_retained_in_inosine_containing_pre_mRNAs_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0261-4189&date=1995&volume=14&issue=13&spage=3236 DB - PRIME DP - Unbound Medicine ER -