Use this URL to cite or link to this record in EThOS:
Title: Genetic screens of RNA binding proteins identify a role for N6-methyladenosine in promoting B cell differentiation
Author: Turner, David
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2020
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Post-transcriptional regulation of gene expression is mediated in part by RNA binding proteins (RBPs). Roles for RBPs have emerged in the immune system but remain largely unexplored. My project utilised high-throughput genetic screens to identify roles for RBPs in lymphocytes. Initially, I generated custom sgRNA libraries targeting RBPs to facilitate CRISPR/Cas9 mediated gene knockout screens in either human or mouse contexts. Then, I employed these reagents to identify roles for RBPs in redox signalling, B cell lymphomagenesis, CD8 T cell activation, and B cell terminal differentiation. These identified over a dozen potential avenues of future investigation into the roles of RBPs in lymphocytes. I chose to further investigate the role of the RNA modification N6-methyladenosine (m6A) in B cells. This work demonstrated a role for the m6A binding protein Ythdf2 in promoting B cell terminal differentiation, independently of a role in proliferation or survival. In the future, I hope to validate an in vivo role for Ythdf2; and further elucidate the in vitro molecular mechanism.
Supervisor: Turner, Martin ; Hodson, Daniel Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: RNA binding proteins ; CRISPR/Cas9 ; m6A ; YTHDF2