Event date:
Aug 25 2021 12:00 pm

Deciphering the role of Rbfox2 in miRNA processing at Dicer level

Dr. Muhammad Afzal Dogar
Menahil Mehmood
Zoom Meetings (Online)
PhD Synopsis defense
Project: 1Deciphering the role of Rbfox2 in miRNA processing at Dicer level.
miRNAs are 20-22 nucleotide short non-coding RNAs that play important roles in gene regulation. Most miRNAs are transcribed by RNA polymerase and are then processed by a nuclear RNase III enzyme Drosha resulting in hairpin loop structures which are exported out of the nucleus via Exportin -5. In cytoplasm a second processing step catalyzed by another RNase III enzyme Dicer produces the miRNA/miRNA* duplex which is incorporated into the RNA induced silencing complex (RISC). RISC incorporates one of the two strands as the guide strand. Based on seed sequence complementarity of the guide strand the miRNA/RISC complex directs the post-transcriptional silencing of the target mRNAs either through transcript degradation of translational repression. Several RNA binding proteins (RBPs) are crucial for the biogenesis of precise mature miRNAs. Rbfox2, a well-known splicing factor and an RNA binding protein that recognizes and binds to canonical GCAUG sequence has also been implicated in miRNA biogenesis. Several miRNAs house the typical GCAUG Fox Binding Element (FBE) in their terminal loop regions and thus are strong targets for FOX2 mediated processing effects. Our study aims at investigating the role of FOX2 in miRNA processing at Dicer level particularly for miR-20b, a member of the oncomir family. The study will provide insight into how the gene expression programs are regulated by complex networks between RBPs, miRNAs and the target mRNAs.

Project 2:RBFOX2 mediated non-canonical G to A editing of miR-32
Certain modifications take place in the RNA after transcription. About 112 different types of RNA modification have been observed. However, one unique type of RNA modification alters the sequence of RNA transcript making it different from the corresponding DNA sequence. This type of modification is termed as RNA editing. It has now been established that RNA editing occurs routinely in the cell and includes processes such as cytidine (C) to uracil (U) and adenosine (A) to inosine (I) nucleotide modifications resulting from deamination reactions and nucleotide insertions and deletions. These deamination reactions are carried out by specific deaminases such as ADARs and APOBECs. Besides canonical RNA editing there have been a few reports on a less common type of RNA editing event i.e. the conversion of G to A. This G to A conversion cannot be simply explained by a deamination reaction and therefore must involve some other enzymes. There have also been a few studies reporting the occurrence of canonical RNA editing in miRNA. For example A to I editing has been reported for pri-mir-142 and pri-mir-22. The aim of this study is to identify non-canonical G to A editing in miRNAs and to work out the precise mechanism leading to such changes. The study will also delve into the role of Rbfox2 in G to A editing events of miRNAs containing typical FBE. This study will set the stage for new paradigms of RNA editing in the context of miRNAs.

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