The Role of RNA Helicase RHAU in Immunoglobulin Class Switch Recombination

<p>B cells alter the expression of immunoglobulin isotypes through a process known as class switch recombination (CSR). In these cells, activation induced cytidine deaminase (AID) binds Gquadruplex (G4) switch transcripts, which serve as guide RNAs to target AID to the immunoglobulin heavy chain switch (S) regions in the DNA for CSR. Sequence alignment revealed homology between the AID G4 binding domain and the RNA helicase associated with AU-rich element (RHAU) specific motif (RSM), which allows RHAU binding to G4 RNAs and subsequent unwinding of G4 RNA into single-stranded transcripts. We hypothesize that RHAU functions in CSR by binding G4 S transcripts and resolving them into linear transcripts which base pair with the immunoglobulin heavy chain S region DNA to localize AID specifically to the recombining S regions. To test this hypothesis, we conditionally deleted floxed<em> Rhau</em> alleles in mouse B cells using a CD23-cre transgene. <em>Rhau</em>^D/D B cells show decreased <em>in vitro</em> CSR to IgG1 and <em>Rhau</em>^D/D mice display decreased IgG1, IgA, and IgG3 titers, suggesting that RHAU regulates CSR.</p>

Name thesis:degree_name

Master of Science (M.S.)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2022

Author dc:creator

• Jean Guillaume, Sabine

Contributors dc:contributor

• Bao Vuong

• AID
• G-quadruplex RNA
• Switch transcripts
• RHAU
• DHX36
• B cells
• Biology
• Life Sciences
• Medicine and Health Sciences

Repository record dc:identifier

https://academicworks.cuny.edu/cc_etds_theses/1004

OAI identifier oai:identifier

oai:academicworks.cuny.edu:cc_etds_theses-2071