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TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA

The replication-dependent histone mRNAs end in a stem–loop instead of the poly(A) tail present at the 3′ end of all other cellular mRNAs. Following processing, the 3′ end of histone mRNAs is trimmed to 3 nucleotides (nt) after the stem–loop, and this length is maintained by addition of nontemplated...

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Autores principales: Lackey, Patrick E., Welch, Joshua D., Marzluff, William F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066620/
https://www.ncbi.nlm.nih.gov/pubmed/27609902
http://dx.doi.org/10.1261/rna.058107.116
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author Lackey, Patrick E.
Welch, Joshua D.
Marzluff, William F.
author_facet Lackey, Patrick E.
Welch, Joshua D.
Marzluff, William F.
author_sort Lackey, Patrick E.
collection PubMed
description The replication-dependent histone mRNAs end in a stem–loop instead of the poly(A) tail present at the 3′ end of all other cellular mRNAs. Following processing, the 3′ end of histone mRNAs is trimmed to 3 nucleotides (nt) after the stem–loop, and this length is maintained by addition of nontemplated uridines if the mRNA is further trimmed by 3′hExo. These mRNAs are tightly cell-cycle regulated, and a critical regulatory step is rapid degradation of the histone mRNAs when DNA replication is inhibited. An initial step in histone mRNA degradation is digestion 2–4 nt into the stem by 3′hExo and uridylation of this intermediate. The mRNA is then subsequently degraded by the exosome, with stalled intermediates being uridylated. The enzyme(s) responsible for oligouridylation of histone mRNAs have not been definitively identified. Using high-throughput sequencing of histone mRNAs and degradation intermediates, we find that knockdown of TUT7 reduces both the uridylation at the 3′ end as well as uridylation of the major degradation intermediate in the stem. In contrast, knockdown of TUT4 did not alter the uridylation pattern at the 3′ end and had a small effect on uridylation in the stem–loop during histone mRNA degradation. Knockdown of 3′hExo also altered the uridylation of histone mRNAs, suggesting that TUT7 and 3′hExo function together in trimming and uridylating histone mRNAs.
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spelling pubmed-50666202017-11-01 TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA Lackey, Patrick E. Welch, Joshua D. Marzluff, William F. RNA Article The replication-dependent histone mRNAs end in a stem–loop instead of the poly(A) tail present at the 3′ end of all other cellular mRNAs. Following processing, the 3′ end of histone mRNAs is trimmed to 3 nucleotides (nt) after the stem–loop, and this length is maintained by addition of nontemplated uridines if the mRNA is further trimmed by 3′hExo. These mRNAs are tightly cell-cycle regulated, and a critical regulatory step is rapid degradation of the histone mRNAs when DNA replication is inhibited. An initial step in histone mRNA degradation is digestion 2–4 nt into the stem by 3′hExo and uridylation of this intermediate. The mRNA is then subsequently degraded by the exosome, with stalled intermediates being uridylated. The enzyme(s) responsible for oligouridylation of histone mRNAs have not been definitively identified. Using high-throughput sequencing of histone mRNAs and degradation intermediates, we find that knockdown of TUT7 reduces both the uridylation at the 3′ end as well as uridylation of the major degradation intermediate in the stem. In contrast, knockdown of TUT4 did not alter the uridylation pattern at the 3′ end and had a small effect on uridylation in the stem–loop during histone mRNA degradation. Knockdown of 3′hExo also altered the uridylation of histone mRNAs, suggesting that TUT7 and 3′hExo function together in trimming and uridylating histone mRNAs. Cold Spring Harbor Laboratory Press 2016-11 /pmc/articles/PMC5066620/ /pubmed/27609902 http://dx.doi.org/10.1261/rna.058107.116 Text en © 2016 Lackey et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Article
Lackey, Patrick E.
Welch, Joshua D.
Marzluff, William F.
TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA
title TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA
title_full TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA
title_fullStr TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA
title_full_unstemmed TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA
title_short TUT7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mRNA
title_sort tut7 catalyzes the uridylation of the 3′ end for rapid degradation of histone mrna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066620/
https://www.ncbi.nlm.nih.gov/pubmed/27609902
http://dx.doi.org/10.1261/rna.058107.116
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