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Mycobacteriophages as Incubators for Intein Dissemination and Evolution

Inteins are self-splicing protein elements that are mobile at the DNA level and are sporadically distributed across microbial genomes. Inteins appear to be horizontally transferred, and it has been speculated that phages may play a role in intein distribution. Our attention turns to mycobacteriophag...

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Detalles Bibliográficos
Autores principales: Kelley, Danielle S., Lennon, Christopher W., Belfort, Marlene, Novikova, Olga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050341/
https://www.ncbi.nlm.nih.gov/pubmed/27703073
http://dx.doi.org/10.1128/mBio.01537-16
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author Kelley, Danielle S.
Lennon, Christopher W.
Belfort, Marlene
Novikova, Olga
author_facet Kelley, Danielle S.
Lennon, Christopher W.
Belfort, Marlene
Novikova, Olga
author_sort Kelley, Danielle S.
collection PubMed
description Inteins are self-splicing protein elements that are mobile at the DNA level and are sporadically distributed across microbial genomes. Inteins appear to be horizontally transferred, and it has been speculated that phages may play a role in intein distribution. Our attention turns to mycobacteriophages, which infect mycobacteria, where both phage and host harbor inteins. Using bioinformatics, mycobacteriophage genomes were mined for inteins. This study reveals that these mobile elements are present across multiple mycobacteriophage clusters and are pervasive in certain genes, like the large terminase subunit TerL and a RecB-like nuclease, with the majority of intein-containing genes being phage specific. Strikingly, despite this phage specificity, inteins localize to functional motifs shared with bacteria, such that intein-containing genes have similar roles, like hydrolase activity and nucleic acid binding, indicating a global commonality among intein-hosting proteins. Additionally, there are multiple insertion points within active centers, implying independent invasion events, with regulatory implications. Several phage inteins were shown to be splicing competent and to encode functional homing endonucleases, important for mobility. Further, bioinformatic analysis supports the potential for phages as facilitators of intein movement among mycobacteria and related genera. Analysis of catalytic intein residues finds the highly conserved penultimate histidine inconsistently maintained among mycobacteriophages. Biochemical characterization of a noncanonical phage intein shows that this residue influences precursor accumulation, suggesting that splicing has been tuned in phages to modulate generation of important proteins. Together, this work expands our understanding of phage-based intein dissemination and evolution and implies that phages provide a context for evolution of splicing-based regulation.
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spelling pubmed-50503412016-10-13 Mycobacteriophages as Incubators for Intein Dissemination and Evolution Kelley, Danielle S. Lennon, Christopher W. Belfort, Marlene Novikova, Olga mBio Research Article Inteins are self-splicing protein elements that are mobile at the DNA level and are sporadically distributed across microbial genomes. Inteins appear to be horizontally transferred, and it has been speculated that phages may play a role in intein distribution. Our attention turns to mycobacteriophages, which infect mycobacteria, where both phage and host harbor inteins. Using bioinformatics, mycobacteriophage genomes were mined for inteins. This study reveals that these mobile elements are present across multiple mycobacteriophage clusters and are pervasive in certain genes, like the large terminase subunit TerL and a RecB-like nuclease, with the majority of intein-containing genes being phage specific. Strikingly, despite this phage specificity, inteins localize to functional motifs shared with bacteria, such that intein-containing genes have similar roles, like hydrolase activity and nucleic acid binding, indicating a global commonality among intein-hosting proteins. Additionally, there are multiple insertion points within active centers, implying independent invasion events, with regulatory implications. Several phage inteins were shown to be splicing competent and to encode functional homing endonucleases, important for mobility. Further, bioinformatic analysis supports the potential for phages as facilitators of intein movement among mycobacteria and related genera. Analysis of catalytic intein residues finds the highly conserved penultimate histidine inconsistently maintained among mycobacteriophages. Biochemical characterization of a noncanonical phage intein shows that this residue influences precursor accumulation, suggesting that splicing has been tuned in phages to modulate generation of important proteins. Together, this work expands our understanding of phage-based intein dissemination and evolution and implies that phages provide a context for evolution of splicing-based regulation. American Society for Microbiology 2016-10-04 /pmc/articles/PMC5050341/ /pubmed/27703073 http://dx.doi.org/10.1128/mBio.01537-16 Text en Copyright © 2016 Kelley et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Kelley, Danielle S.
Lennon, Christopher W.
Belfort, Marlene
Novikova, Olga
Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_full Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_fullStr Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_full_unstemmed Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_short Mycobacteriophages as Incubators for Intein Dissemination and Evolution
title_sort mycobacteriophages as incubators for intein dissemination and evolution
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050341/
https://www.ncbi.nlm.nih.gov/pubmed/27703073
http://dx.doi.org/10.1128/mBio.01537-16
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