Alternative splicing produces high levels of noncoding isoforms of bHLH transcription factors during development (Retracted article. See vol. 25, pg. 1344, 2011)

作者：Kanadia Rahul N; Cepko Constance L^*

来源：Genes & Development, 2010, 24(3): 229-234.

DOI：10.1101/gad.1847110

• Alternative splicing
• Math5
• Ngn3
• noncoding
• retina
• progenitor cells
• post-mitotic cells

During development, multiple cell types within a tissue often arise from a common pool of progenitor cells (PCs). PCs typically expand in number, while simultaneously producing post-mitotic cells (PMCs). This balance is partly regulated by transcription factors that are expressed within PCs, such as the basic helix-loop-helix (bHLH) gene mouse atonal homolog 7 (Math5), which is expressed in retinal PCs. Here we report that alternative splicing (AS) of Math5 serves as another layer of regulation of Math5 activity. Specifically, Math5, a single exon gene, is alternatively spliced such that the major isoform lacks the entire coding sequence. Similarly, neurogenin 3 (Ngn3), a Math5 paralog expressed in pancreatic PCs, is also alternatively spliced such that the major isoform fails to code for Ngn3 protein. The consequence of reducing the abundance of protein-coding isoforms is likely crucial, as we found that introduction of coding isoforms leads to a reduction in cycling PCs. Thus, AS can limit the number of PCs expressing key regulatory proteins that control PC expansion versus PMC production.

• 出版日期2010-2-1