Elimination of Calm1 long 3'-UTR mRNA isoform by CRISPR-Cas9 gene editing impairs dorsal root ganglion development and hippocampal neuron activation in mice.

RNA
B. BaePedro Miura

Abstract

The majority of mouse and human genes are subject to alternative cleavage and polyadenylation (APA), which most often leads to the expression of two or more alternative length 3' untranslated region (3'-UTR) mRNA isoforms. In neural tissues, there is enhanced expression of APA isoforms with longer 3'-UTRs on a global scale, but the physiological relevance of these alternative 3'-UTR isoforms is poorly understood. Calmodulin 1 (Calm1) is a key integrator of calcium signaling that generates short (Calm1-S) and long (Calm1-L) 3'-UTR mRNA isoforms via APA. We found Calm1-L expression to be largely restricted to neural tissues in mice including the dorsal root ganglion (DRG) and hippocampus, whereas Calm1-S was more broadly expressed. smFISH revealed that both Calm1-S and Calm1-L were subcellularly localized to neural processes of primary hippocampal neurons. In contrast, cultured DRG showed restriction of Calm1-L to soma. To investigate the in vivo functions of Calm1-L, we implemented a CRISPR-Cas9 gene editing strategy to delete a small region encompassing the Calm1 distal poly(A) site. This eliminated Calm1-L expression while maintaining expression of Calm1-S Mice lacking Calm1-L (Calm1ΔL/ΔL ) exhibited disorganized DRG migration...Continue Reading

References

Jul 20, 1989·Journal of Molecular Biology·H Nojima
Jan 1, 1988·Annual Review of Cell Biology·N M Le Douarin, J Smith
May 8, 1980·Nature·A R Means, J R Dedman
Nov 15, 1996·Science·M Tessier-Lavigne, C S Goodman
Jan 1, 1997·Journal of Neuroscience Methods·M L FanarragaJ Deschamps
Mar 21, 2001·Journal of Neurobiology·Y S KimM F VanBerkum
Apr 2, 2005·Nature Reviews. Neuroscience·Zhengui Xia, Daniel R Storm
Jan 24, 2007·Nature Reviews. Neuroscience·Frédéric Marmigère, Patrik Ernfors
Jul 31, 2007·The EMBO Journal·Andrew C Lin, Christine E Holt
Mar 20, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zhiping P PangThomas C Südhof
Jul 27, 2010·Expert Opinion on Drug Discovery·Giorgia Melli, Ahmet Höke
Nov 19, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Krishna H ZivrajChristine E Holt
Jun 4, 2011·Molecular and Cellular Neurosciences·Liam J DrewJoseph A Gogos
Jul 28, 2011·Cold Spring Harbor Perspectives in Biology·Anna M Hagenston, Hilmar Bading
Jun 23, 2012·Genome Research·Igor UlitskyDavid P Bartel
Jul 31, 2012·Neuron·Rotem Ben-Tov PerryMike Fainzilber
Mar 23, 2013·Genome Research·Pedro MiuraEric C Lai
Mar 30, 2013·Nature Methods·Florian MuellerChristophe Zimmer
Apr 27, 2013·Nucleic Acids Research·Stanislav BellaousovDavid H Mathews
May 15, 2013·The FEBS Journal·Anders B SorensenMichael T Overgaard
Oct 2, 2013·The Journal of Cell Biology·Toshiaki ShigeokaChristine E Holt
Jun 7, 2014·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Pedro MiuraEric C Lai
Sep 5, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ye ZhangJian Qian Wu
Sep 18, 2014·Frontiers in Systems Neuroscience·Dasuni S Alwis, Ramesh Rajan

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Apr 13, 2021·Wiley Interdisciplinary Reviews. RNA·Isabel Pereira-Castro, Alexandra Moreira
May 7, 2021·ELife·Sibylle Mitschka, Christine Mayr

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