INVESTIGADORES
DE LA MATA Manuel
artículos
Título:
How Slow RNA Polymerase II Elongation Favors Alternative Exon Skipping.
Autor/es:
DUJARDIN G, LAFAILLE C, DE LA MATA M, MARASCO LE, MUÑOZ MJ, LE JOSSIC-CORCOS C, CORCOS L, KORNBLIHTT AR.
Revista:
MOLECULAR CELL
Editorial:
CELL PRESS
Referencias:
Año: 2014 vol. 54 p. 683 - 690
ISSN:
1097-2765
Resumen:
Splicing is functionally coupled to transcription, linking the rate of
RNA polymerase II (Pol II) elongation and the ability of splicing
factors to recognize splice sites (ss) of various strengths. In most
cases, slow Pol II elongation allows weak splice sites to be recognized,
leading to higher inclusion of alternative exons. Using CFTR
alternative exon 9 (E9) as a model, we show here that slowing down
elongation can also cause exon skipping by promoting the recruitment of
the negative factor ETR-3 onto the UG-repeat at E9 3' splice site, which
displaces the constitutive splicing factor U2AF65 from the overlapping
polypyrimidine tract. Weakening of E9 5' ss increases ETR-3 binding at
the 3' ss and subsequent E9 skipping, whereas strengthening of the 5' ss
usage has the opposite effect. This indicates that a delay in the
cotranscriptional emergence of the 5' ss promotes ETR-3 recruitment and
subsequent inhibition of E9 inclusion.