IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
capítulos de libros
Título:
Coupling between Transcription and Alternative Splicing
Autor/es:
SCHOR IE; GOMEZ ACUÑA LI; KORNBLIHTT AR
Libro:
RNA and Cancer
Editorial:
Springer
Referencias:
Año: 2012;
Resumen:
Alternative splicing is currently considered a key mechanism in the generation of higher eukaryotes complexity as it not only increases proteomic diversity, but it also contributes to tissue identity and dynamic proteome modulation. Recent evidence shows that the scenario of alternative splicing regulation is far more complex than the classical picture of an already transcribed pre-mRNA that will be spliced in different ways according to regulatory RNA-binding splicing factors. Introns are efficiently removed while transcripts are still being synthesized, supporting the idea of co-trasncriptional splicing. Moreover, there is a compelling evidence of a functional coupling between these two processes. Co-transcriptionality is thought to improve splicing efficiency and kinetics by directing the nascent pre-mRNA into proper spliceosome assembly and favoring splicing factor recruitment and exon/intron definition. The carboxy-terminal domain (CTD) of the RNA pol II seems to be critical for this functional coupling. Two non-exclusive models have been proposed to account for transcription influence on alternative splicing: in the recruitment model, promoters and pol II status affect the recruitment to the transcribing gene of splicing factors or bi-functional factors acting on both transcription and splicing; in the kinetic model, differences in the elongation rate of pol II modifies the timing in which splicing sites are presented to the splicing machinery, and thus the outcome of alternative splicing decisions. In addition to the transcribing machinery, the template for transcription can also affect both the pol II elongation dynamics and the recruitment of auxiliary factors. Therefore, it is no surprising that chromatin structure, especially in the internal regions of genes, had emerged as a novel regulator of pre-mRNA processing. Although we do not have definitive evidence of transcriptionally-coupled alternative splicing alterations responsible for tumor development or cancer pathogenesis, the evidence accumulated for several years calls for  re-consideringprevious reports of cancer-associated splicing patterns in the light of transcription-splicing coupling.