University of Pittsburgh Department of Biological Sciences Presents:
Friday Noon Seminar Series 2017-2018
Graduate Student: Hiba Al-Ashtal
Making Ends Meet: The role of the LARP1 La-Module in RNA recognition
The La-related protein (LARP) superfamily is a diverse family of RNA binding proteins that are characterized by an N-terminal La-Module. The La-Module is comprised of two RNA-binding domains, a La Motif (LAM) and an RNA recognition motif (RRM), which function synergistically to engage an array of RNAs. Sequence and structural changes to the La-Module lead to unique RNA binding specificity and biological function. For example, genuine La, the prototypical LARP, utilizes its La-Module to engage the 3’UUU-OH of premature tRNAs in order to facilitate their folding and maturation. In stark contrast, the LARP6 La-Module has been repurposed to engage a stem loop within the 5’UTR of collagen mRNAs to regulate their translation. LARP1 is the most divergent member of the LARP family, and has been implicated in the stability and translation of mRNAs encoding for the translation machinery.
To date, the RNA binding partners and function of the LARP1 La-Module remain elusive. The long-term goal of my project aims to characterize the RNA-binding specificities of the LARP1 La-Module. Due its association with Poly(A)-binding protein, we hypothesized that the LARP1 La-Module has evolved to bind poly(A) RNA; we found that the La-Module indeed binds poly(A) RNA. Interestingly, we found that, in addition to binding poly(A) RNA, the LARP1 La-Module simultaneously engages the 5’terminal oligpyrimidine (TOP) motif characteristic of mRNAs that encode for translation machinery. Therefore, we propose that the La-Module of LARP1 helps to circularize these mRNAs to regulate their stability and translation.
Friday, January 26, 2017
A219B Langley Hall
12:00 PM Seminar