Biologjia Online

Approximately 60% of human genes undergo alternative splicing. This alternative splicing allows a single gene to encode dozens, and in some cases even thousands, of different protein isoforms, vastly increasing the diversity of the proteome that can be encoded by a limited number of genes. In mammals, only a fraction of the regulatory proteins (splicing factors) involved in controlling alternative splicing have been identified, and little is known about the mechanisms by which these factors regulate splicing. In this paper, Naganari Ohkura and colleagues identify an enzyme called coactivator-associated arginine methyltransferase 1 (CARM1), which is known to contribute to transcriptional activation by methylating histone H3, as a regulator of alternative splicing.

Ohkura and colleagues offer two novel observations about CARM1: 1) they identify new splicing variants of CARM1, which are expressed in a tissue-specific manner, and 2) they report the exciting discovery that one of the new splicing variants, CARM1-v3, binds to the U1 small nuclear ribonucleoprotein particle (snRNP) component of the spliceosome and alters splicing patterns of mRNAs. Interestingly, a C-terminal CARM1-v3 region, which is unique to this particular splice variant, is responsible for the splicing regulation function, whereas the methyltransferase activity of CARM1 is dispensable. These findings add CARM1 to the list of components that can modulate 5' splice site selection and provide a new mechanism by which transcription and processing, two critical steps in gene expression, may be coordinated.