Accepted: A placental mammal-specific microRNA cluster acts as a natural brake for sociability in mice

Did you ever wonder how ncRNAs could influence behavior ?

Then, you would probably like to read on it in our new EMBO reports manuscript by

Lackinger, M., Sungur, A.Ö., Daswani, R., Soutschek, M., Bicker, S., Stemmler, L., Wüst, T., Fiore, R., Dieterich, C., Schwarting, R.K.W., Wöhr, M. and Schratt, G.

Aberrant synaptic function is thought to underlie social deficits in neurodevelopmental disorders such as autism and schizophrenia. microRNAs have been shown to regulate synapse development and plasticity, their potential involvement in the control of social behaviour in mammals however remains unexplored. Here we show that deletion of the large placental mammal-specific miR379-410 cluster in mice unexpectedly leads to hypersocial behaviour, which is accompanied by increased excitatory synaptic transmission and exaggerated expression of ionotropic glutamate receptor complexes in the hippocampus. Bioinformatics further allowed us to identify five “hub” microRNAs whose deletion accounts for a large part of the upregulation of excitatory synaptic genes, including Cnih2, Dlgap3, Prr7 and Src. Thus, miR379-410 is a natural brake for sociability and interfering with specific members of this cluster could represent a therapeutic strategy for social deficits in neurodevelopmental disorders.

Methods for Analysis of Circular RNAs: No Tautology

We are excited to announce funding by EMBO for implementing a workshop on circular RNAs.

Organizers: Vladimir Benes (main), Irene Bozzoni, Marie-Laure Baudet and
Christoph Dieterich
Category: EMBO Practical Course
Title: EMBO Practical Course: Methods for analysis of circular RNAs: No tautology
Dates: 17 November 2019 – 22 November 2019
Location: DE–Heidelberg

https://www.embl.de/training/events/2019/CIR19-01/index.html

 

Guardians of the transcriptome

Our new article on “Exon junction complexes suppress spurious splice sites to safeguard transcriptome integrity” is in press and will appear in Molecular Cell beginning of November. Congratulations to the team of authors: 

Volker Boehm1, Thiago Britto-Borges2,3, Anna-Lena Steckelberg1,4, Kusum K. Singh1,5, Jennifer V. Gerbracht1, Elif Gueney1, Lorea Blazquez6,7, Janine Altmüller8,9,10, Christoph Dieterich2,3, Niels H. Gehring1,11


Productive splicing of human pre-mRNAs requires the correct selection of authentic splice sites (SS) from the large pool of potential SS. Although SS consensus sequence and splicing regulatory proteins are known to influence SS usage, the mechanisms ensuring the effective suppression of cryptic SS are insufficiently explored. Here, we find that many aberrant exonic SS are efficiently silenced by the exon junction complex (EJC), a multi-protein complex that is deposited on spliced mRNA near the exon-exon junction. Upon depletion of EJC proteins, cryptic SS are de-repressed, leading to the mis-splicing of a broad set of mRNAs. Mechanistically, the EJC-mediated recruitment of the splicing regulator RNPS1 inhibits cryptic 5′SS usage, while the deposition of the EJC core directly masks reconstituted 3′SS, thereby precluding transcript disintegration. Thus, the EJC protects the transcriptome of mammalian cells from inadvertent loss of exonic sequences and safeguards the expression of intact, full length mRNAs.

Flexbar 3.0 – SIMD and multicore parallelization

Motivation:

High throughput sequencing machines can process many samples in a single run. For Illumina systems, sequencing reads are barcoded with an additional DNA tag that is contained in the respective sequencing adapters. The recognition of barcode and adapter sequences is hence commonly needed for the analysis of next generation sequencing data. Flexbar performs demultiplexing based on barcodes and adapter trimming for such data. read more…

A microRNA-129-5p/Rbfox crosstalk coordinates homeostatic downscaling of excitatory synapses – New paper

Abstract: Synaptic downscaling is a homeostatic mechanism that allows neurons to reduce firing rates during chronically elevated network activity. Although synaptic downscaling is important in neural circuit development and epilepsy, the underlying mechanisms are poorly described. We performed small RNA profiling in picrotoxin (PTX)-treated hippocampal neurons, a model of synaptic downscaling. Thereby, we identified eight microRNAs (miRNAs) that were increased in response to PTX, including miR-129-5p, whose inhibition blocked synaptic downscaling in vitro and reduced epileptic seizure severity in vivo Using transcriptome, proteome, and bioinformatic analysis, we identified the calcium pump Atp2b4 and doublecortin (Dcx) as miR-129-5p targets. Restoring Atp2b4 and Dcx expression was sufficient to prevent synaptic downscaling in PTX-treated neurons. Furthermore, we characterized a functional crosstalk between miR-129-5p and the RNA-binding protein (RBP) Rbfox1. In the absence of PTX, Rbfox1 promoted the expression of Atp2b4 and Dcx. Upon PTX treatment, Rbfox1 expression was downregulated by miR-129-5p, thereby allowing the repression of Atp2b4 and Dcx. We therefore identified a novel activity-dependent miRNA/RBP crosstalk during synaptic scaling, with potential implications for neural network homeostasis and epileptogenesis.

Find me on Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/28487411