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Genes Dev. 2010 Feb 1;24(3):229-34. doi: 10.1101/gad.1847110. Epub 2010 Jan 15.

Alternative splicing produces high levels of noncoding isoforms of bHLH transcription factors during development.

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  • 1Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA; and Department of Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

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.

PMID:
20080942
[PubMed - indexed for MEDLINE]
PMCID:
PMC2811824
Free PMC Article
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