Al-Ashtal, Hiba
(2020)
Making Ends Meet: Role of the LARP1 La-Module in TOP mRNA Recognition.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
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 synergistically engage RNA. Sequence and structural changes to the La-Module lead to unique RNA binding specificity and biological function. For example, the La-Module of Genuine La, the prototypical LARP, binds the 3’UUU-OH of pre-tRNAs to facilitate their folding and maturation. In contrast, the LARP6 La-Module binds a stem-loop within the 5’UTR of collagen mRNAs to regulate their translation. LARP1 is the most divergent member of the LARP superfamily, and has been implicated in the stability and translation of mRNAs encoding the translation machinery.
The RNA binding partners and function of the LARP1 La-Module remain elusive. Because it associates 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 discovered that it simultaneously engages the 5’ terminal oligopyrimidine (TOP) motif characteristic of mRNAs that encode the translation machinery. We hypothesize that through binding to features at the 5’ and 3’ end of TOP mRNAs, the 5’ TOP motif and poly(A) tails, the La-Module may aid mRNA circularization to regulate TOP mRNA translation regulation. In addition, multivalent interactions between the La-Module and mRNAs may aid sequestration of TOP mRNAs to stress granules and processing-bodies during translation repression in response to stress.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
8 June 2020 |
| Date Type: |
Publication |
| Defense Date: |
2 March 2020 |
| Approval Date: |
8 June 2020 |
| Submission Date: |
18 March 2020 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
153 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
LARP1 TOP mRNA translation |
| Date Deposited: |
08 Jun 2020 15:44 |
| Last Modified: |
08 Jun 2022 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/38345 |
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