MITF Isoforms- Insights from an RNA-Seq study

Isoforms play an essential role in enhancing evolutionary diversity. Microphthalmia inducing transcription factor (MITF) is known to be a master regulator of pigmentation response and a lineage survival oncogene in melanoma. MITF is also known to have several functional isoforms, the -M form is known to be essential for the melanocyte lineage and is the most widely studied in the context of pigmentation biology and melanoma development and progression. This study uses an RNA seq approach in order to examine changes in the transcriptional profile of Skmel28 cells when treated with double strand break inducing compound and/or after knockdown of MITF. Intriguingly, we observe an enrichment of MITF-Mdel isoform on both MITF knockdown as well as on induction of DNA damage. Closer examination revealed that the siRNA used for the study targets all MITF isoforms except MITF-Mdel. We also observe a protein band at the size predicted for the protein. We therefore hypothesize a potential redundant role for the MITF-Mdel isoform and a potential novel role in DNA double strand beak response.