How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing?

NAFTELBERG, S.; AST, G.; LEV-MAOR, G.; HOLLANDER, D.; KORNBLIHTT, A. R.

TRENDS IN GENETICS

ELSEVIER SCIENCE LONDON

Lugar: Londres; Año: 2016 vol. 32 p. 596 - 606

0168-9525

The splice sites (SSs) delimiting an intron are brought together in the earlieststep of spliceosome assembly yet it remains obscure how SS pairing occurs,especially when introns are thousands of nucleotides long. Splicing occurs invivo in mammals within minutes regardless of intron length, implying that SSpairing can instantly follow transcription. Also, factors required for SS pairing,such as the U1 small nuclear ribonucleoprotein (snRNP) and U2AF65, associatewith RNA polymerase II (RNAPII), while nucleosomes preferentially bind exonicsequences and associate with U2 snRNP. Based on recent publications, weassume that the 50 SS-bound U1 snRNP can remain tethered to RNAPII untilcomplete synthesis of the downstream intron and exon. An additional U1 snRNPthen binds the downstream 50 SS, whereas the RNAPII-associated U2AF65binds the upstream 30 SS to facilitate SS pairing along with exon definition.Next, the nucleosome-associated U2 snRNP binds the branch site to advancesplicing complex assembly. This may explain how RNAPII and chromatin areinvolved in spliceosome assembly and how introns lengthened during evolutionwith a relatively minimal compromise in splicing.