Final Report Summary - ERNBPTC (Expression regulatory networks: beyond promoters and transcription control)
The aims of this project were to further the understanding of post-transcriptional regulation, with a focus on the control of protein translation and the control of mRNA degradation. A particular aspect of our research was the global coordination between levels of control, particularly how transcription affects transcription degradation and how translation, transcription and degradation are inter-connected. We worked with several species, including yeast, human and bacteria. We combined towards our aims experimental genomics and bioinformatics and modeling.
Our main discoveries include:
1. We discovered universal design principle of protein translation efficiency, called the “ramp”. In this design proteins are encoded with codons that correspond to low abundance tRNAs at their 5’ regions. This design was suggested to act to lower costs of protein proteon production in cells
2. We discovered a dual translation program that operates in mammals in times of cellular proliferation and differentiation. The two programs consist of distinct sets of tRNAs and codons. Cancer appears to utilize the proliferation program
3. We discovered a system for coordinated transcription and mRNA degradation. The mechanism is based on subunits of the polymerase that are imprinted on transcripts co-transcritionally. This mechanism explains how coupling production and degradation can control the kinetics of the transcriptome in response to stress
4. We discovered a new sequence
language” that governs the effect of 3’ UTR sequences on RNA levels. This was done by a novel usage of a library of sequence variants that examined the effect of various 3’ UTR motifs on gene expression
5. We found a novel coupling mechanism between ribosome movement on mRNA and points of cleavage of the RNA. We found how ribosomal positioning code may govern the patter on cleavage of RNA
Our main discoveries include:
1. We discovered universal design principle of protein translation efficiency, called the “ramp”. In this design proteins are encoded with codons that correspond to low abundance tRNAs at their 5’ regions. This design was suggested to act to lower costs of protein proteon production in cells
2. We discovered a dual translation program that operates in mammals in times of cellular proliferation and differentiation. The two programs consist of distinct sets of tRNAs and codons. Cancer appears to utilize the proliferation program
3. We discovered a system for coordinated transcription and mRNA degradation. The mechanism is based on subunits of the polymerase that are imprinted on transcripts co-transcritionally. This mechanism explains how coupling production and degradation can control the kinetics of the transcriptome in response to stress
4. We discovered a new sequence
language” that governs the effect of 3’ UTR sequences on RNA levels. This was done by a novel usage of a library of sequence variants that examined the effect of various 3’ UTR motifs on gene expression
5. We found a novel coupling mechanism between ribosome movement on mRNA and points of cleavage of the RNA. We found how ribosomal positioning code may govern the patter on cleavage of RNA