Roles of Non-coding RNAs in the Control of the Coupling Between Transcription and Alternative Splicing
Mariano Alló and Alberto R. Kornblihtt
from: Non-coding RNAs and Epigenetic Regulation of Gene Expression: Drivers of Natural Selection (Edited by: Kevin V. Morris). Caister Academic Press, U.K. (2012)
Since the discovery of splicing in 1977, alternative splicing was seen for more than two decades as an interesting mechanism to generate protein diversity but with limited genome-wide influence because it was thought to affect only 20% of mammalian genes. The sequencing of the human and other mammals' genomes in the early 2000's together with more recent high throughput analyses of splicing isoforms generated a renewed interest in alternative splicing. We know now that alternative splicing affects more than 90% of human genes, that normal and pathological cell differentiation not only depends on differential gene transcription but also on alternative splicing patterns, that mutations that either create or abolish alternative splicing regulatory sequences, named splicing enhancers and silencers, are a widespread source of human disease and that alternative splicing factors can be misregulated in cancer. The relationship between splicing and non-coding RNAs has emerged recently in the middle of an avalanche of papers showing how chromatin context could affect splicing choices. The convergence of these previously unrelated areas (non-coding RNAs, chromatin and splicing) has presented a novel and intriguing scenario that will be covered in this chapter, starting with a brief overview of transcription and splicing introducing the understanding of how these processes could be modulated by external factors. Then we will focus on our work using non-coding small RNAs (ncsRNAs) to regulate alternative splicing in human cells. Finally, we will discuss the evidence supporting the potential activity of endogenous non-coding RNAs as modulators of alternative splicing read more ...