Role of M1BP, a transcriptional pausing factor in JNK-mediated cell death during eye development

Role of M1BP, a transcriptional pausing factor in JNK-mediated cell death during eye development

Presenter(s)

Hannah Darnell, Anuradha Chimata Venkatakrishnan

Comments

Presentation: 1:15-2:30 p.m., Kennedy Union Ballroom

Description

During development, transcriptional regulation is a fundamental mechanism(s) to regulate differential gene expression. Recently, we have shown that M1BP, a transcriptional pausing factor and a functional homolog of ZKSCAN3, promotes cell survival in developing eyes by suppressing wingless (wg). We performed a forward genetic screen, to identify other targets of M1BP mediated transcriptional repression that may contribute to eye suppression phenotype. We identified members of Jun-amino-terminal-(NH2)-Kinase (JNK) signaling pathway as modifiers of the “no-eye” or “reduced-eye” phenotype of MIBPRNAi. We hypothesized that M1BP may promote cell survival in developing eyes by downregulating JNK signaling. Using the Gal4-UAS system, we modulated both JNK signaling components along with downregulation of M1BP function and assayed their role in cell survival during eye development. We found that downregulation of M1BP results in activation of JNK signaling which in turns activates both apoptosis as well as autophagy. Activation of JNK signaling enhances M1BPRNAi phenotype and downregulation of JNK signaling rescues the M1BPRNAi “no-eye” phenotype. Secondly, blocking cell death or autophagy alone genetically does not completely rescue M1BPRNAi phenotype of “no-eye”. Finally, downregulation of M1BP along with blocking both apoptosis and autophagy resulted in a significant rescue of the M1BPRNAi ”no-eye” phenotype. Here, we present the role and mechanism by which transcriptional pausing promote cell survival in developing eye.

Publication Date

4-19-2023

Project Designation

Graduate Research

Primary Advisor

Amit Singh, Madhuri Kango-Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Institutional Learning Goals

Scholarship

Role of M1BP, a transcriptional pausing factor in JNK-mediated cell death during eye development

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