Control of alternative pre-mRNA splicing by RNA Pol II elongation: faster is not always better.
The realization that the mammalian proteomic complexity is achieved with a limited number of genes demands a better understanding of alternative splicing regulation. Promoter control of alternative splicing was originally described by our group in studies performed on the fibronectin gene. Recently, other labs extended our findings to the cystic fibrosis, CD44 and CGRP genes strongly supporting a coupling between transcription and pre-mRNA splicing. A possible mechanism that would fit in these results is that the promoter itself is responsible for recruiting splicing factors, such as SR proteins, to the site of transcription, possibly through transcription factors that bind the promoter or the transcriptional enhancers. An alternative model, discussed more extensively in this review, involves modulation of RNA pol II (pol II) elongation rate. The model is supported by findings that cis- and trans- acting factors that modulate pol II elongation on a particular template also provoke changes in the alternative splicing balance of the encoded mRNAs.
Nogués
Guadalupe
G
Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II. (C1428EHA) Buenos Aires, Argentina.
Kadener
Sebastián
S
Cramer
Paula
P
de la Mata
Manuel
M
Fededa
Juan Pablo
JP
Blaustein
Matiás
M
Srebrow
Anabella
A
Kornblihtt
Alberto R
AR
D017398:Alternative Splicing; D000818:Animals; D008957:Models, Genetic; D012319:RNA Polymerase II / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D014158:Transcription, Genetic
D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012319:RNA Polymerase II