Elaine Nguyen on identifying molecular determinants of LARP1-RNA interaction

Elaine Nguyen, Berman Lab

Identifying molecular determinants of LARP1-RNA interaction

Gene expression is carefully regulated at the transcriptional and post-transcriptional levels to facilitate proper development and cell homeostasis. In the cell, mRNAs are always coated in RNA-binding proteins (RBP) that mediate the steps in the mRNA life cycle from processing to degradation. La-related protein 1 (LARP1) is an RBP that has been implicated in mRNA stability and translational control of a class of transcripts called 5’ TOPs (5’ terminal oligopyrimidine). 5’ TOPs encode all ribosomal proteins that constitute the ribosome as well as other translation-related factors. However, knockdown of LARP1 has shown that it does not affect translation regulation of all TOPs equally. In vitrobinding assays corroborate that the C-terminal DM15 region of LARP1 preferentially binds some 5’ TOPs but not others. A structure of DM15 with a short oligo corresponding to a TOP motif has shown us the RNA binding surface, but does not provide sufficient information for explaining the molecular reasons for preferential binding displayed by DM15. How and why does LARP1 bind some 5’ TOPs and not others? I have begun dissecting this question using biochemical and structural techniques to define RNA and LARP1 features that are required for interaction. I found that this interaction is 5’ TOP motif length-dependent, and I have begun interrogating sequence specificity.Additionally, preliminary data support that RNA protects amino acids C-terminal to the DM15 region, which could suggest that RNA promotes the folding of the remaining C-terminal residues. Elucidating the molecular basis for LARP1 recognition of cognate mRNAs is fundamental to understanding the role of LARP1 in mediating translational control of 5’ TOPs.

Friday, November 16th

12 PM

A219B Langley Hall


16 Nov 2018

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A219B Langley Hall