A novel actin mRNA splice variant regulates ACTG1 expression.

Cytoplasmic actins are abundant, ubiquitous proteins in nucleated cells. However, actin expression is regulated in a tissue- and development-specific manner. We identified a novel cytoplasmic-γ-actin (Actg1) transcript that includes a previously unidentified exon (3a). Inclusion of this exon introdu...

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Autores principales: Meghan C Drummond, Karen H Friderici
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/bfa2306ca844495eb6c90789fcf69a4f
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spelling oai:doaj.org-article:bfa2306ca844495eb6c90789fcf69a4f2021-11-18T06:21:44ZA novel actin mRNA splice variant regulates ACTG1 expression.1553-73901553-740410.1371/journal.pgen.1003743https://doaj.org/article/bfa2306ca844495eb6c90789fcf69a4f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098136/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Cytoplasmic actins are abundant, ubiquitous proteins in nucleated cells. However, actin expression is regulated in a tissue- and development-specific manner. We identified a novel cytoplasmic-γ-actin (Actg1) transcript that includes a previously unidentified exon (3a). Inclusion of this exon introduces an in-frame termination codon. We hypothesized this alternatively-spliced transcript down-regulates γ-actin production by targeting these transcripts for nonsense-mediated decay (NMD). To address this, we investigated conservation between mammals, tissue-specificity in mice, and developmental regulation using C2C12 cell culture. Exon 3a is 80% similar among mammals and varies in length from 41 nucleotides in humans to 45 in mice. Though the predicted amino acid sequences are not similar between all species, inclusion of exon 3a consistently results in the in the introduction of a premature termination codon within the alternative Actg1 transcript. Of twelve tissues examined, exon 3a is predominantly expressed in skeletal muscle, cardiac muscle, and diaphragm. Splicing to include exon 3a is concomitant with previously described down-regulation of Actg1 in differentiating C2C12 cells. Treatment of differentiated C2C12 cells with an inhibitor of NMD results in a 7-fold increase in exon 3a-containing transcripts. Therefore, splicing to generate exon 3a-containing transcripts may be one component of Actg1 regulation. We propose that this post-transcriptional regulation occurs via NMD, in a process previously described as "regulated unproductive splicing and translation" (RUST).Meghan C DrummondKaren H FridericiPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 10, p e1003743 (2013)
institution DOAJ
collection DOAJ
language EN
topic Genetics
QH426-470
spellingShingle Genetics
QH426-470
Meghan C Drummond
Karen H Friderici
A novel actin mRNA splice variant regulates ACTG1 expression.
description Cytoplasmic actins are abundant, ubiquitous proteins in nucleated cells. However, actin expression is regulated in a tissue- and development-specific manner. We identified a novel cytoplasmic-γ-actin (Actg1) transcript that includes a previously unidentified exon (3a). Inclusion of this exon introduces an in-frame termination codon. We hypothesized this alternatively-spliced transcript down-regulates γ-actin production by targeting these transcripts for nonsense-mediated decay (NMD). To address this, we investigated conservation between mammals, tissue-specificity in mice, and developmental regulation using C2C12 cell culture. Exon 3a is 80% similar among mammals and varies in length from 41 nucleotides in humans to 45 in mice. Though the predicted amino acid sequences are not similar between all species, inclusion of exon 3a consistently results in the in the introduction of a premature termination codon within the alternative Actg1 transcript. Of twelve tissues examined, exon 3a is predominantly expressed in skeletal muscle, cardiac muscle, and diaphragm. Splicing to include exon 3a is concomitant with previously described down-regulation of Actg1 in differentiating C2C12 cells. Treatment of differentiated C2C12 cells with an inhibitor of NMD results in a 7-fold increase in exon 3a-containing transcripts. Therefore, splicing to generate exon 3a-containing transcripts may be one component of Actg1 regulation. We propose that this post-transcriptional regulation occurs via NMD, in a process previously described as "regulated unproductive splicing and translation" (RUST).
format article
author Meghan C Drummond
Karen H Friderici
author_facet Meghan C Drummond
Karen H Friderici
author_sort Meghan C Drummond
title A novel actin mRNA splice variant regulates ACTG1 expression.
title_short A novel actin mRNA splice variant regulates ACTG1 expression.
title_full A novel actin mRNA splice variant regulates ACTG1 expression.
title_fullStr A novel actin mRNA splice variant regulates ACTG1 expression.
title_full_unstemmed A novel actin mRNA splice variant regulates ACTG1 expression.
title_sort novel actin mrna splice variant regulates actg1 expression.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/bfa2306ca844495eb6c90789fcf69a4f
work_keys_str_mv AT meghancdrummond anovelactinmrnasplicevariantregulatesactg1expression
AT karenhfriderici anovelactinmrnasplicevariantregulatesactg1expression
AT meghancdrummond novelactinmrnasplicevariantregulatesactg1expression
AT karenhfriderici novelactinmrnasplicevariantregulatesactg1expression
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