Page 13 - Rappaport Institute Magazine 2024

BIOCHEMISTRY
10-11
Investigating the RNA dynamics during global transcription stress
Transcription is a fundamental process all living organisms use to convert static DNA information into a highly dynamic network of gene products. However, certain stress conditions, such as DNA damage, anti-cancer treatments, and starvation, significantly limit the ability of cells to express their genes. If transcription is a vital process required for life, how do mammalian cells deal with transcriptional shortage? Can they survive periods of insufficient transcription, or shall they die? Our group studies the impact of multiple conditions leading to global transcription stress (GTS) on RNA homeostasis. We found that exposure to GTS leads to the RNA stress response, including inhibition of mRNA translation, significant stabilization of the existing transcripts, and shortening of poly(A) tails. Strikingly, affected cells often manage to survive prolonged periods of insufficient transcription. Currently, we are investigating the role of the RNA stress response in cell survival during GTS and its effect on protein homeostasis. For example, we employ cutting-edge biochemical and genomic approaches to understand whether anti-cancer treatments alter the cellular localization of mRNAs. We anticipate our studies will help better understand the molecular mechanisms enabling cancer cells to survive treatments and develop relapsed tumors.
Selected Publications
Boris Slobodin, PhD Senior Lecturer of Biochemistry
PhD, 2011 – Weizmann Institute of Science, Israel
ˆ Slobodin B#, Sehrawat U., Lev A., Ogran A., Fraticelli D., Hayat D., Zuckerman B., Ulitsky I., Ben-Shmuel A., Bar-David E., Levy H., Dikstein R#. (2022) Cap-independent translation and a precisely localized RNA sequence enable SARS-CoV-2 to control host translation and escape anti-viral response. Nucleic Acids Research, 50(14) 8080-8092. PMID: 35849342
ˆ Slobodin B.#, Bahat A., Sehrawat U., Becker-Herman S., Zuckerman B., Weiss AN., Han R., Elkon R., Agami R., Ulitsky I., Shachar I., and Dikstein R#. (2020) Transcription dynamics regulate poly(A) tails and expression of the RNA degradation machinery to balance mRNA levels. Mol Cell, 78(3) 434-444.e5. PMID: 32294471
ˆ Slobodin B*#, Han R*, Calderone V, Vrielink JA, Loayza-Puch F, Elkon R, Agami R#. (2017) Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation. Cell, 2017 Apr 6;169(2):326-337.e12. PMID:28388414
Grants and Awards
ISF - personal grant
Rappaport Institute short-term grant Collaborators
Dr. Monika Burness, University of Michigan
boris.sl@technion.ac.il
Boris Slobodin Lab
Upon treatment of HeLa cells with anti-cancer compound Irinotecan (right panel), mRNAs exhibit enhanced nuclear localization as compared to control conditions (left panel).
Red = mRNAs, blue = DNA (nuclei), green = cell periphery (actin).