How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing?. Issue 10 (October 2016)

• Record Type: Journal Article
• Authors: Hollander, Dror; Naftelberg, Shiran; Lev-Maor, Galit; Kornblihtt, Alberto R.; Ast, Gil
• Is Part Of: Trends in genetics. Volume 32:Issue 10(2016)
• Page Start: 596
• Page End: 606
• Publication Date: 2016-10
• Subjects: Genetics -- Periodicals; 576.5
• DOI: 10.1016/j.tig.2016.07.003
• Languages: English
• ISSNs: 0168-9525

Abstract

Abstract : The splice sites (SSs) delimiting an intron are brought together in the earliest step of spliceosome assembly yet it remains obscure how SS pairing occurs, especially when introns are thousands of nucleotides long. S plicing occurs in vivo in mammals within minutes regardless of intron length, implying that SS pairing can instantly follow transcription. Also, factors required for SS pairing, such as the U1 small nuclear ribonucleoprotein (snRNP) and U2AF65, associate with RNA polymerase II (RNAPII), while nucleosomes preferentially bind exonic sequences and associate with U2 snRNP. Based on recent publications, we assume that the 5′ SS-bound U1 snRNP can remain tethered to RNAPII until complete synthesis of the downstream intron and exon. An additional U1 snRNP then binds the downstream 5′ SS, whereas the RNAPII-associated U2AF65 binds the upstream 3′ SS to facilitate SS pairing along with exon definition. Next, the nucleosome-associated U2 snRNP binds the branch site to advance splicing complex assembly. This may explain how RNAPII and chromatin are involved in spliceosome assembly and how introns lengthened during evolution with a relatively minimal compromise in splicing. Trends: The splicing rates of very long mammalian introns and of short ones are similar. It is therefore baffling how spatially distant splice sites (SSs) are rapidly brought into proximity in vivo when introns are thousands of nucleotides long. There is much evidence concerning the functional associations between splicing factors and RNA polymerase II (RNAPII) as well as between splicing factors and chromatin. Since splicing factors involved in the identification of the 5′ and 3′ SSs associate with RNAPII, SS pairing could potentially occur closely following the synthesis of long introns as they are still attached to chromatin via RNAPII. Functional associations between splicing factors and chromatin would later promote splicing factor recruitment to the RNA to advance the splicing reaction.