TranslationRegCode - Cracking the Translation Regulatory Code 

About the project

Organisms across all kingdoms share several systems that are essential to life, one of the most central being protein synthesis. Living in a continuously changing environment, cells need to constantly respond to various environmental cues and change their protein landscape. In extreme cases, cells globally shut down protein synthesis and upregulate stress-protective proteins.

Mechanisms of translational repression or selective enhancement of stress-induced proteins have been characterized, but their effects were demonstrated on an individual mRNA basis. Which target mRNAs are translationally regulated in response to different environmental cues, and what are the cis-regulatory elements involved, largely remain as open questions. Using ribosome footprint profiling, we recently discovered a novel mode of translational control in stress, underscoring the potential of new technologies to uncover novel regulatory mechanisms. But while transcription cis-regulatory elements have been thoroughly mapped in the past decade, and splicing regulatory elements are accumulating, the identification of translation cis-regulatory elements is lagging behind.

Here we propose to crack the mammalian translation regulatory code, and close this long-standing gap. We present a novel interdisciplinary framework to comprehensively identify translation cis-regulatory elements, and map their mRNAs targets in a variety of cellular perturbations. Importantly, we plan to explore mechanisms underlying novel cis-regulatory elements, and create the first genome-wide functionally

annotated translation regulatory code.

The translation regulatory code will map targets of existing mechanisms and shed light on newly identified

pathways that play a role in stress-induced translational control. The proposed project is an imperative

stepping stone to understanding translational regulation by cis-regulatory elements, opening new avenues in

the functional genomics research of translational control.

The ERC team

Dr. Reut Shalgi
PI
reutshalgi@technion.ac.il
+972-4-8295388
Dr. Flonia Levy-Adam
Lab manager
laflonia@technion.ac.il
+972-4-8295395
Flonia.JPG
Amal Younis
MD/PHd student
amal.unis13@outlook.com
+972-4-8295395
Anatoly Meller
PhD student
anatoly.junior@gmail.com
+972-4-8295395
תמונה_שני_edited.jpg
Shani Hadar
MSc student
shanihadar@campus.technion.ac.il 
+972-4-8295395
IMG-20190206-WA0027.jpg
Naseeb Saida
MD/PhD student
+972-4-8295395

Publications

  • Meller, A. and Shalgi R. The aging proteostasis decline: From nematode to human. Experimental Cell Research. 2021 January. PDF.

  • Sabath, N.*, Levy-Adam, F.*, Younis, A.*, Rozales, K., Meller, A., Hadar, S., Soueid-Baumgarten, S., Shalgi, R. Cellular proteostasis decline in human senescence. PNAS. 2020 Dec. PDF. *Equal contribution.

  • Nir Gonen#, Anatoly Meller#, Niv Sabath and Reut Shalgi. Amino acid biosynthesis regulation during ER stress is coupled to protein expression demands. iScience. 2019 July. # These authors contributed equally to the work.

  • Nir Gonen, Niv Sabath, Christopher B. Burge, and Reut Shalgi. Widespread PERK-dependent repression of ER targets in response to ER stress. Scientific Reports. 2019 March

  • Yuval Wiesel, Niv Sabath and Reut Shalgi. DoGFinder: a software for the discovery and quantification of readthrough transcripts from RNA-seq. BMC Genomics, 2018 Aug. 

  • Anna Vilborg, Niv Sabath, Yuval Weisel, Jenny Nathans, Flonia Levi-Adam, Therese A. Yario, Joan A. Steitz, and Reut Shalgi. Comparative analysis reveals genomic features of stress-induced transcriptional readthrough. PNAS, 2017 Sept. 

Conference presentations

  • Reut Shalgi, "Cellular proteostasis collapse and decoupling between transcription and translation regulation in mammalian senescence", RNA-COSI, ISMB 2019, Bazel, Switzerland, July 2019.

  • Reut Shalgi, "Cellular proteostasis collapse in mammalian senescence", Gordon Research Conference: Stress Proteins in Growth, Development and Disease, Lucca, Italy, June 2019. Invited.

  • Reut Shalgi, "Cellular proteostasis collapse in mammalian senescence", EMBO Protein quality control: From mechanisms to disease, Mallorca, Spain, April 2019.

  • Reut Shalgi, "Cellular proteostasis collapse in mammalian senescence", EMBO Genome Dynamics in Neuroscience and Aging workshop, Herzelia, Israel. April 2019. 

  • Reut Shalgi, "Coupling between amino acid biosynthesis and protein expression demands in the adaptive UPR", FASEB Protein Folding in the Cell, Olean, NY, USA. July 2018.

  • Reut Shalgi, “Widespread regulation of transcriptional readthrough is a hallmark of the mammalian proteotoxic stress response“, CSHL Eukaryotic mRNA processing, Cold Spring Harbor, NY, USA, 2017

  • Reut Shalgi, "Widespread regulation of transcriptional readthrough is a hallmark of the mammalian proteotoxic stress response", RNA-SIG, ISMB, Prague, Czech Republic. 2017