FUNCTIONAL ANALYSIS OF CFIM PROTEINS IN GERM CELL ALTERNATIVE POLYADENYLATION

University Of Rhode Island, Kingston RI

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Male infertility accounts for one third of the couples who seek treatment for failure to conceive. Recent research has shown that aberrant regulation of gene expression during spermatogenesis causes decreased sperm function. Alternative polyadenylation, the generation of cell-specific messenger RNA (mRNA) isoforms by poly (A) tail addition, is a hallmark of gene regulation during spermatogenesis. Cleavage factor I (CFIm), comprised of the NUDT21/CPSF5 and CPSF6 subunits, are polyadenylation RNA binding proteins that are highly enriched in male germ cells and contain a shorter 3'untranslated region (UTR) generated by alternative polyadenylation. While the CFIm proteins can direct differential polyadenylation site selection of somatic cell mRNAs, the role of CFIm in producing testis-specific transcripts is unknown. Using RNA interference, we will develop functional studies in a male germ cell line to investigate the hypothesis that CFIm subunits are necessary for male germ cell-specific alternative polyadenylation and subsequent protein translation. Development of a functional assay in this male germ cell line will also establish a model for studying gene expression during spermatogenesis. A greater understanding the molecular and cellular regulation of sperm production holds promise in developing new treatments for male infertility.