TY  - JOUR
A1  - Salehi, Saeede
A1  - Zare, Abdolhossein
A1  - Prezza, Gianluca
A1  - Bader, Jakob
A1  - Schneider, Cornelius
A1  - Fischer, Utz
A1  - Meissner, Felix
A1  - Mann, Matthias
A1  - Briese, Michael
A1  - Sendtner, Michael
T1  - Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr
JF  - Nature Communications
N2  - The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol including axons and growth cones of motoneurons, and that depletion of cytosolic Ptbp2 affects axon growth. We identify Ptbp2 as a major interactor of the 3’ UTR of Hnrnpr mRNA encoding the RNA-binding protein hnRNP R. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus suggest a mechanism whereby cytosolic Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein.
KW  - molecular neuroscience
KW  - RNA-binding proteins
KW  - RNA transport
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357639
VL  - 14
ER  - 
TY  - JOUR
A1  - Prezza, Gianluca
A1  - Ryan, Daniel
A1  - Mädler, Gohar
A1  - Reichardt, Sarah
A1  - Barquist, Lars
A1  - Westermann, Alexander J.
T1  - Comparative genomics provides structural and functional insights into Bacteroides RNA biology
JF  - Molecular Microbiology
N2  - Bacteria employ noncoding RNA molecules for a wide range of biological processes, including scaffolding large molecular complexes, catalyzing chemical reactions, defending against phages, and controlling gene expression. Secondary structures, binding partners, and molecular mechanisms have been determined for numerous small noncoding RNAs (sRNAs) in model aerobic bacteria. However, technical hurdles have largely prevented analogous analyses in the anaerobic gut microbiota. While experimental techniques are being developed to investigate the sRNAs of gut commensals, computational tools and comparative genomics can provide immediate functional insight. Here, using Bacteroides thetaiotaomicron as a representative microbiota member, we illustrate how comparative genomics improves our understanding of RNA biology in an understudied gut bacterium. We investigate putative RNA-binding proteins and predict a Bacteroides cold-shock protein homolog to have an RNA-related function. We apply an in silico protocol incorporating both sequence and structural analysis to determine the consensus structures and conservation of nine Bacteroides noncoding RNA families. Using structure probing, we validate and refine these predictions and deposit them in the Rfam database. Through synteny analyses, we illustrate how genomic coconservation can serve as a predictor of sRNA function. Altogether, this work showcases the power of RNA informatics for investigating the RNA biology of anaerobic microbiota members.
KW  - BT_1884
KW  - cold-shock protein
KW  - GibS
KW  - RNA-binding proteins
KW  - secondary structure
KW  - 6S RNA
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259594
VL  - 117
IS  - 1
ER  -