Alternatively spliced MBNL1 isoforms exhibit differential influence on enhancing brown adipogenesis

In this study, we first identified the discriminative expression and splicing profiles of the muscleblind-like 1 (MBNL1) gene in postnatal brown adipose tissues (BATs) compared to those of embryonic BATs. A shift in the MBNL1+ex 5 isoform 7 (MBNL17) to MBNL1−ex 5 isoform 1 (MBNL11) was characterized throughout BAT development or during the in vitro browning of pre-WAs, 3T3-L1 cells. The interplay between MBNL1 and the exonic CCUG motif constitutes an autoregulatory mechanism for excluding MBNL1 exon 5. The simultaneous association of RNA-binding motif protein 4a (RBM4a) with exonic and intronic CU elements collaboratively mediates the skipping of MBNL1 exon 5. Overexpressing the MBNL11 isoform exhibited a more-prominent effect than that of the MBNL17 isoform on programming its own transcripts and beige cell-related splicing events in a CCUG motif-mediated manner. In addition to splicing regulation, overexpression of the MBNL11 and MBNL17 isoforms differentially enhanced beige adipogenic signatures of 3T3-L1 cells. Our findings demonstrated that MBNL1 constitutes an emerging and autoregulatory mechanism involved in development of beige cells.

Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - November 13, 2019 Category: Genetics & Stem Cells Source Type: research