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Feedback regulation of small RNA processing by the cleavage product

Many bacterial small RNAs (sRNAs) are processed resulting in variants with roles potentially distinct from the primary sRNAs. In Enterobacteriaceae sRNA GlmZ activates expression of glmS by base-pairing when the levels of glucosamine-6-phosphate (GlcN6P) are low. GlmS synthesizes GlcN6P, which is re...

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Autores principales: Durica-Mitic, Svetlana, Görke, Boris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602413/
https://www.ncbi.nlm.nih.gov/pubmed/31116083
http://dx.doi.org/10.1080/15476286.2019.1612693
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author Durica-Mitic, Svetlana
Görke, Boris
author_facet Durica-Mitic, Svetlana
Görke, Boris
author_sort Durica-Mitic, Svetlana
collection PubMed
description Many bacterial small RNAs (sRNAs) are processed resulting in variants with roles potentially distinct from the primary sRNAs. In Enterobacteriaceae sRNA GlmZ activates expression of glmS by base-pairing when the levels of glucosamine-6-phosphate (GlcN6P) are low. GlmS synthesizes GlcN6P, which is required for cell envelope biosynthesis. When dispensable, GlmZ is cleaved by RNase E in the base-pairing sequence. Processing requires protein RapZ, which binds GlmZ and recruits RNase E by interaction. Cleavage is counteracted by the homologous sRNA GlmY, which accumulates upon GlcN6P scarcity and sequesters RapZ. Here, we report a novel role for a processed sRNA. We observed that processing of GlmZ is never complete in vivo. Even upon RapZ overproduction, a fraction of GlmZ remains full-length, while the 5ʹ cleavage product (GlmZ*) accumulates. GlmZ* retains all elements required for RapZ binding. Accordingly, GlmZ* can displace full-length GlmZ from RapZ and counteract processing in vitro. To mimic GlmZ* in vivo, sRNA chimeras were employed consisting of foreign 3ʹ ends including a terminator fused to the 3ʹ end of GlmZ*. In vitro, these chimeras perform indistinguishable from GlmZ*. Expression of the chimeras in vivo inhibited processing of endogenous GlmZ, causing moderate upregulation of GlmS synthesis. Hence, accumulation of GlmZ* prevents complete GlmZ turnover. This mechanism may serve to adjust a robust glmS basal expression level that is buffered against fluctuations in RapZ availability.
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spelling pubmed-66024132019-07-08 Feedback regulation of small RNA processing by the cleavage product Durica-Mitic, Svetlana Görke, Boris RNA Biol Research Paper Many bacterial small RNAs (sRNAs) are processed resulting in variants with roles potentially distinct from the primary sRNAs. In Enterobacteriaceae sRNA GlmZ activates expression of glmS by base-pairing when the levels of glucosamine-6-phosphate (GlcN6P) are low. GlmS synthesizes GlcN6P, which is required for cell envelope biosynthesis. When dispensable, GlmZ is cleaved by RNase E in the base-pairing sequence. Processing requires protein RapZ, which binds GlmZ and recruits RNase E by interaction. Cleavage is counteracted by the homologous sRNA GlmY, which accumulates upon GlcN6P scarcity and sequesters RapZ. Here, we report a novel role for a processed sRNA. We observed that processing of GlmZ is never complete in vivo. Even upon RapZ overproduction, a fraction of GlmZ remains full-length, while the 5ʹ cleavage product (GlmZ*) accumulates. GlmZ* retains all elements required for RapZ binding. Accordingly, GlmZ* can displace full-length GlmZ from RapZ and counteract processing in vitro. To mimic GlmZ* in vivo, sRNA chimeras were employed consisting of foreign 3ʹ ends including a terminator fused to the 3ʹ end of GlmZ*. In vitro, these chimeras perform indistinguishable from GlmZ*. Expression of the chimeras in vivo inhibited processing of endogenous GlmZ, causing moderate upregulation of GlmS synthesis. Hence, accumulation of GlmZ* prevents complete GlmZ turnover. This mechanism may serve to adjust a robust glmS basal expression level that is buffered against fluctuations in RapZ availability. Taylor & Francis 2019-05-22 /pmc/articles/PMC6602413/ /pubmed/31116083 http://dx.doi.org/10.1080/15476286.2019.1612693 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Durica-Mitic, Svetlana
Görke, Boris
Feedback regulation of small RNA processing by the cleavage product
title Feedback regulation of small RNA processing by the cleavage product
title_full Feedback regulation of small RNA processing by the cleavage product
title_fullStr Feedback regulation of small RNA processing by the cleavage product
title_full_unstemmed Feedback regulation of small RNA processing by the cleavage product
title_short Feedback regulation of small RNA processing by the cleavage product
title_sort feedback regulation of small rna processing by the cleavage product
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602413/
https://www.ncbi.nlm.nih.gov/pubmed/31116083
http://dx.doi.org/10.1080/15476286.2019.1612693
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