MEC-8 regulates alternative splicing of unc-52 transcripts in C. elegans hypodermal cells

Caroline A. Spike, Andrew A. Davies, Jocelyn E. Shaw, Robert K. Herman

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Previous work has shown that C. elegans MEC-8 is a putative RNA-binding protein that promotes specific alternative splices of unc-52 transcripts. unc-52 encodes homologs of mammalian perlecan that are located extracellularly between muscle and hypodermis and are essential for muscle development in both embryos and larvae. We show that MEC-8 is a nuclear protein found in hypodermis at most stages of development and not in most late embryonic or larval body-wall muscle. We have also found that overexpression of MEC-8 in hypodermis but not muscle can suppress certain unc-52 mutant phenotypes. These are unexpected results because it has been proposed that UNC-52 is produced exclusively by muscle. We have constructed various tissue-specific unc-52 minigenes fused to a gene for green fluorescent protein that have allowed us to monitor tissue-specific mec-8-dependent alternative splicing; we show that mec-8 must be expressed in the same cell type as the unc-52 minigene in order to regulate its expression, supporting the view that MEC-8 acts directly on unc-52 transcripts and that UNC-52 must be synthesized primarily by the hypodermis. Indeed, our analysis of unc-52 genetic mosaics has shown that the focus of unc-52 action is not in body-wall muscle but most likely is in hypodermis.

Original languageEnglish (US)
Pages (from-to)4999-5008
Number of pages10
JournalDevelopment
Volume129
Issue number21
StatePublished - Nov 2002

Keywords

  • Alternative splicing
  • Mec-8
  • Perlecan
  • RRM
  • Unc-52

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