Date of Award

Spring 5-12-2018

Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

Advisor

Robert E. Braun

Second Committee Member

Mary Ann Handel

Third Committee Member

Gregory Cox

Additional Committee Members

Gregory Carter

Viravuth Yin

Abstract

Micro RNAs (miRNAs), which are ~22 nucleotide (nt) long RNA molecules and several RNA binding proteins (RBPs) engage in an RNA dependent post-transcriptional gene silencing process known as RNA interference (RNAi). In the canonical miRNA biogenesis pathway, an enzyme known as DICER cleaves the ~70nt pre-miRNA to a ~22nt long miRNA that is loaded into the RNAi effector mechanism, the RNA induced silencing complex (RISC).

Several in vitro studies provide suggestive evidence that mammalian double stranded RNA binding proteins (dsRBPs), such as TARBP2, act as DICER cofactors in miRNA processing and RISC loading to promote RNAi activity. A screen attempting to identify translational regulators of the murine Protamine1 gene identified TARBP2 as a potential translation regulator. It is unknown if TARBP2 has a role in miRNA biogenesis in vivo, or if the translation regulation of Prm1 during murine spermatogenesis is dependent on TARBP2 mediated miRNA biogenesis.

Murine embryos with a constitutive null allele of Tarbp2 and adult mice with a germ cell-specific loss of TARBP2 were generated to lead to understanding of the role of TARBP2 in miRNA biogenesis and TARBP2 mediated post-transcriptional gene regulation during spermatogenesis. Here, I describe that TARBP2 regulate biogenesis of a sub-set of miRNAs during murine embryonic development and spermatogenesis. Also, the role of TARBP2 dependent miRNAs in post-transcriptional regulation of gene expression during murine spermatogenesis will be discussed.

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