Project

hnRNP; protein-RNA complexes; NMR spectroscopy; RNA binding domains; RNA editing; Translation regulation; Non coding RNA; IRES

Lead
Understanding the molecular mechanisms regulating gene expression at the posttranscriptional level is a major question in molecular biology, defects in these mechanisms being at the origin of many genetic diseases. This proposal focuses on two of these processes: RNA editing and translation regulation.
Lay summary
Understanding the molecular mechanisms regulating gene expression at the posttranscriptional level is a major question in molecular biology, defects in these mechanisms being at the origin of many genetic diseases. This proposal focuses on two of these processes: RNA editing and translation regulation. RNA editing occurs in human by single base deamination, C to U or A to I. These changes create codons for different amino acids, stop codons or even new splice-sites allowing larger protein diversity. A to I editing is catalysed at specific sites by ADARs whose substrate recognition mechanisms are still unclear. Translation regulation plays a major role in many diverse cellular processes such as carbon metabolism, viral replication, apoptosis, embryonic development, cell differentiation and synapse activation. We focus here on aspects of translational regulation under the control of protein binding the mRNA 5'or 3'UTRs. At the 5'UTR, we are interested in how RsmA/CsrA proteins control bacterial translation initiation and how hnRNP proteins (PTB and hnRNP C) and UNR help IRES-mediated translation initiation of viral and cellular mRNAs. At the 3'UTR, we are interested in how RNA binding proteins like the human CPEBs, hnRNP L and EPRS stabilize mRNAs to regulate translation.We are proposing here to determine the NMR structures of several key protein-RNA complexes involved in RNA editing and translation regulation. First, we aim at understanding how ADAR2 recognizes two of its substrates, second, how the bacterial translation repressor RsmE recognizes certain 5'UTR mRNA and also several non-coding RNA like RsmZ, third, how PTB, hnRNP C and Unr binds IRESes to facilitate or repress translation initiation, fourth, how CPEB and CPEB3 both bind dormant mRNA to regulate their translation and fifth how hnRNP L and EPRS control a riboswitch in VEGFA mRNA.

Direct link to Lay Summary

Last update: 23.12.2012

Active participation

Number	Title	Start	Funding scheme

Understanding the molecular mechanisms regulating gene expression at the posttranscriptional level is a major question in molecular biology, defects in these mechanisms being at the origin of many genetic diseases. This proposal focuses on two of these processes: RNA editing and translation regulation. RNA editing occurs in human by single base deamination, C to U or A to I. These changes create codons for different amino acids, stop codons or even new splice-sites allowing larger protein diversity. A to I editing is catalysed at specific sites by ADARs whose substrate recognition mechanisms are still unclear. Translation regulation plays a major role in many diverse cellular processes such as carbon metabolism, viral replication, apoptosis, embryonic development, cell differentiation and synapse activation. We focus here on aspects of translational regulation under the control of protein binding the mRNA 5’or 3’UTRs. At the 5’UTR, we are interested in how RsmA/CsrA proteins control bacterial translation initiation and how hnRNP proteins (PTB and hnRNP C) and UNR help IRES-mediated translation initiation of viral and cellular mRNAs. At the 3’UTR, we are interested in how RNA binding proteins like the human CPEBs, hnRNP L and EPRS stabilize mRNAs to regulate translation.We are proposing here to determine the NMR structures of several key protein-RNA complexes involved in RNA editing and translation regulation. First, we aim at understanding how ADAR2 recognizes two of its substrates,, second, how the bacterial translation repressor RsmE recognizes certain 5’UTR mRNA and also several non-coding RNA like RsmZ, third, how PTB, hnRNP C and Unr binds IRESes to facilitate or repress translation initiation, fourth, how CPEB and CPEB3 both bind dormant mRNA to regulate their translation and fifth how hnRNP L and EPRS control a riboswitch in VEGFA mRNA.