An additional short stretch of complementarity between U1 snRNA and the 3′ss region does not mediate an interaction ( Seraphin and Kandels-Lewis 1993). RNA (snRNA), which immediately suggested a mechanism for recognition of the 5′ss ( Fig. Moreover, the “consensus” sequence (comprising,Īt each position, the nucleotide most commonly found there) was complementary to the sequence at the 5′ end of U1 small nuclear 1977), sequences emerged rapidly thereafter and revealed clear similarities among 5′ss. The benefit of sequence information ( Berget et al. Thus, although the original discoveries were made without New, gel-based DNA-sequencing methods transformed molecular biology. The phosphodiester bond at the 3′ splice site (3′ss) and displaces the lariat intron. The phosphodiester bond at the 5′ss and displaces the 5′ exon in the second step, the 3′-hydroxyl group of the 5′ exon attacks In the first step, the 2′-hydroxyl group of the branchpoint adenosine attacks The 5′ss is involved in both steps of splicing. Preconceptions hidden in established models. Review is to emphasize that developing new ideas may involve first the challenge of uprooting commonsense but unsubstantiated New ideas and models are needed for studies on splice site selection. Despite the many insights resulting from such studies over the years, it is clear that our conceptualįrameworks are not yet adequate. Of working out the molecular mechanisms involved provided a foretaste of the complexities awaiting investigations into other The first factors shown to modulate alternative splicing affected 5′ss selection, and the difficulties Identification of the sequences associated with 5′ss triggered the first key insights into splicing mechanisms,Įfforts that are reflected now in the widespread use of genomic methods to quantify the contributions of other sequences and Questions about the mechanisms by which 5′ splice sites (5′ss) are selected are deeply rooted in the history of research on Mechanisms by which the recognition of numerous candidate 5′ss might lead to selection of a single 5′ss and propose that proteinĬomplexes propagate along the exon, thereby changing its physical behavior so as to affect 5′ss selection. Proteins, splicing enhancers, and the relative positions of alternative 5′ss contribute to selection. In addition, we describe the mechanisms by which other snRNAs, regulatory Noncanonical registers such as bulged duplexes. We also discuss recent work demonstrating that U1 snRNA:5′ss helices can accommodate Here we review the history of research on 5′ss selection, highlighting the difficulties of establishing how base-pairing Most 5′ss are recognized by base-pairing with the 5′ end of the U1 small nuclear RNA 5′ Splice sites (5′ss)Īre the critical elements at the 5′ end of introns and are extremely diverse, as thousands of different sequences act as bonaįide 5′ss in the human transcriptome. Splice site selection is fundamental to pre-mRNA splicing and the expansion of genomic coding potential.
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