Towards an RNA Splicing Code.

A long-term goal of our research is to understand the RNA splicing code: how exons and splice sites are identified in primary transcripts, and how this code is altered in cell- and condition-specific alternative splicing. We are focusing on understanding the context-dependent activities and interactions among splicing regulatory elements. We have found that most members of a class of elements known as exonic splicing silencers share a consistent pattern of context-dependent activity, silencing splicing when present in exons, activating splicing when present in introns, and altering splice site choice when present between competing splice sites. Splicing regulatory activity may also depend on splice site strength; we are exploring a pattern in which some intronic splicing enhancers enhance splicing of exons more strongly when 5' splice site (5'ss) strength is weak/moderate than when the 5'ss is either stronger or weaker. We are also using computational approaches to identify pairs of preferentially co-occurring motifs, and have used this approach to identify a pair of intronic motifs that can function cooperatively to silence the splicing of intervening exons. [ABSTRACT FROM AUTHOR]