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Most Human Proteins Made in Both Nucleus and Cytoplasm Turn Over within Minutes

In bacteria, protein synthesis can be coupled to transcription, but in eukaryotes it is believed to occur solely in the cytoplasm. Using pulses as short as 5 s, we find that three analogues – L-azidohomoalanine, puromycin (detected after attaching fluors using ‘click’ chemistry or immuno-labeling),...

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Autores principales: Baboo, Sabyasachi, Bhushan, Bhaskar, Jiang, Haibo, Grovenor, Chris R. M., Pierre, Philippe, Davis, Benjamin G., Cook, Peter R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050049/
https://www.ncbi.nlm.nih.gov/pubmed/24911415
http://dx.doi.org/10.1371/journal.pone.0099346
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author Baboo, Sabyasachi
Bhushan, Bhaskar
Jiang, Haibo
Grovenor, Chris R. M.
Pierre, Philippe
Davis, Benjamin G.
Cook, Peter R.
author_facet Baboo, Sabyasachi
Bhushan, Bhaskar
Jiang, Haibo
Grovenor, Chris R. M.
Pierre, Philippe
Davis, Benjamin G.
Cook, Peter R.
author_sort Baboo, Sabyasachi
collection PubMed
description In bacteria, protein synthesis can be coupled to transcription, but in eukaryotes it is believed to occur solely in the cytoplasm. Using pulses as short as 5 s, we find that three analogues – L-azidohomoalanine, puromycin (detected after attaching fluors using ‘click’ chemistry or immuno-labeling), and amino acids tagged with ‘heavy’ (15)N and (13)C (detected using secondary ion mass spectrometry) – are incorporated into the nucleus and cytoplasm in a process sensitive to translational inhibitors. The nuclear incorporation represents a significant fraction of the total, and labels in both compartments have half-lives of less than a minute; results are consistent with most newly-made peptides being destroyed soon after they are made. As nascent RNA bearing a premature termination codon (detected by fluorescence in situ hybridization) is also eliminated by a mechanism sensitive to a translational inhibitor, the nuclear turnover of peptides is probably a by-product of proof-reading the RNA for stop codons (a process known as nonsense-mediated decay). We speculate that the apparently-wasteful turnover of this previously-hidden (‘dark-matter’) world of peptide is involved in regulating protein production.
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spelling pubmed-40500492014-06-18 Most Human Proteins Made in Both Nucleus and Cytoplasm Turn Over within Minutes Baboo, Sabyasachi Bhushan, Bhaskar Jiang, Haibo Grovenor, Chris R. M. Pierre, Philippe Davis, Benjamin G. Cook, Peter R. PLoS One Research Article In bacteria, protein synthesis can be coupled to transcription, but in eukaryotes it is believed to occur solely in the cytoplasm. Using pulses as short as 5 s, we find that three analogues – L-azidohomoalanine, puromycin (detected after attaching fluors using ‘click’ chemistry or immuno-labeling), and amino acids tagged with ‘heavy’ (15)N and (13)C (detected using secondary ion mass spectrometry) – are incorporated into the nucleus and cytoplasm in a process sensitive to translational inhibitors. The nuclear incorporation represents a significant fraction of the total, and labels in both compartments have half-lives of less than a minute; results are consistent with most newly-made peptides being destroyed soon after they are made. As nascent RNA bearing a premature termination codon (detected by fluorescence in situ hybridization) is also eliminated by a mechanism sensitive to a translational inhibitor, the nuclear turnover of peptides is probably a by-product of proof-reading the RNA for stop codons (a process known as nonsense-mediated decay). We speculate that the apparently-wasteful turnover of this previously-hidden (‘dark-matter’) world of peptide is involved in regulating protein production. Public Library of Science 2014-06-09 /pmc/articles/PMC4050049/ /pubmed/24911415 http://dx.doi.org/10.1371/journal.pone.0099346 Text en © 2014 Baboo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Baboo, Sabyasachi
Bhushan, Bhaskar
Jiang, Haibo
Grovenor, Chris R. M.
Pierre, Philippe
Davis, Benjamin G.
Cook, Peter R.
Most Human Proteins Made in Both Nucleus and Cytoplasm Turn Over within Minutes
title Most Human Proteins Made in Both Nucleus and Cytoplasm Turn Over within Minutes
title_full Most Human Proteins Made in Both Nucleus and Cytoplasm Turn Over within Minutes
title_fullStr Most Human Proteins Made in Both Nucleus and Cytoplasm Turn Over within Minutes
title_full_unstemmed Most Human Proteins Made in Both Nucleus and Cytoplasm Turn Over within Minutes
title_short Most Human Proteins Made in Both Nucleus and Cytoplasm Turn Over within Minutes
title_sort most human proteins made in both nucleus and cytoplasm turn over within minutes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050049/
https://www.ncbi.nlm.nih.gov/pubmed/24911415
http://dx.doi.org/10.1371/journal.pone.0099346
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