9.2 years ago by
Alternative Splicing can be regulated by:
- Cis Elements, which are elements within the gene's boundaries. The typical example are the Exonic/Intronic Splicing Enhancers/Silencer (ESE/ISE/ESS/ISS), and by by definition these elements are inside the gene coordinates.
- Trans Elements, which represents all the regulators encoded somewhere else in the genome. For example, the Spliceosome, the machinery that carries out splicing, is composed by a variety of small proteins; if one of these proteins is overexpressed (or not expressed), this affects the alternative splicing of all the genes that require it for splicing. If you consider this definition, it means that all events of alternative splicing are regulated by elements outside the gene coordinates.
- There it can be also splicing regulatory elements in the promoter of the gene or in the proximity. Some consider these as in trans elements while other consider them as in cis, which probably creates a bit of confusion.
Your question may be better defined as "are there any alternative splicing cis-regulatory elements outside the gene's boundaries?"
Unfortunately I can't give you any reference on cases of regulatory elements outside the promoters and the gene boundaries, but I believe that there are many. Most of the research to date has focused on studying ESEs and ISEs because they are easier to characterize, but this does not mean that there are not other elements involved. From what we know, splicing may be also regulated by DNA methylation, or other signals. Consider that most of the splicing regulation signals are very degenerated and rely on very few bases for being recognized, so it is probable that other unknown signals are involved.
I am not very sure on the answer and I can not find a reference to link to you, but I would say "Yes there are", unfortunately I can't remind any known case at the moment. Most of the research done has focused on