Sneha Mishra
Controlling pervasive transcription during neuronal differentiation
Sneha Mishra, Department of Molecular Biology and Genetics, Aarhus University, has received a Lundbeck Foundation Postdoc grant worth DKK 2,400,000.
About the project
How cells ’determine’ which RNAs to degrade vs. which to prepare for functional tasks, is an unanswered question in molecular biology.
New data from Sneha Mishras host laboratory suggest that non-productive transcription events coincide with low transcription initiation levels; i.e. modestly transcribed RNAs appear to be more susceptible to early termination. To test the universal nature of such regulation, I will in the present project utilise a newly reported mismatch guide RNA/CRISPR-dCas9 system to manipulate transcription initiation levels of selected loci and hereby establish a tuneable system to assay the fate of RNAs expressed from weaker vs. stronger promoters.
Using this system, Sneha Mishra will investigate the underlying mechanism, rationalizing how cells control spurious transcription. The Integrator (INT) complex and the ARS2 protein are implicated in such early transcription termination, which is interesting for neurobiology since mutations in INT subunits and in ARS2 are reported in neurological diseases. Her results will decipher the functional implication of INT and ARS2 in controlling pervasive transcription during neuronal differentiation, which may pave the way for future therapeutic intervention.
