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Widespread posttranscriptional regulation of cotransmission
While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters...
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Published in: | Science advances 2023-06, Vol.9 (22), p.eadg9836-eadg9836 |
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container_end_page | eadg9836 |
container_issue | 22 |
container_start_page | eadg9836 |
container_title | Science advances |
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creator | Chen, Nannan Zhang, Yunpeng Rivera-Rodriguez, Emmanuel J Yu, Albert D Hobin, Michael Rosbash, Michael Griffith, Leslie C |
description | While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in
. We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a "translation-trap" strategy, we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of cotransmission is actively modulated. Posttranscriptional restriction of fast transmitter cotransmission provides a mechanism allowing reversible tuning of neuronal output. |
doi_str_mv | 10.1126/SCIADV.ADG9836 |
format | article |
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. We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a "translation-trap" strategy, we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of cotransmission is actively modulated. Posttranscriptional restriction of fast transmitter cotransmission provides a mechanism allowing reversible tuning of neuronal output.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/SCIADV.ADG9836</identifier><identifier>PMID: 37267358</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Cellular Neuroscience ; Cholinergic Agents ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Neurons - metabolism ; Neuroscience ; SciAdv r-articles ; Sleep - physiology ; Synaptic Transmission - genetics</subject><ispartof>Science advances, 2023-06, Vol.9 (22), p.eadg9836-eadg9836</ispartof><rights>Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2023 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-6c88e653e21167d42305fa8b47ab147642fa96116a9b9c4393b520cd833042243</citedby><cites>FETCH-LOGICAL-c391t-6c88e653e21167d42305fa8b47ab147642fa96116a9b9c4393b520cd833042243</cites><orcidid>0000-0002-4899-525X ; 0000-0003-3164-9876 ; 0000-0003-3366-1780 ; 0000-0001-7805-9668 ; 0009-0009-1919-3336 ; 0000-0001-6014-0193 ; 0000-0002-3483-6186</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413644/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413644/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,2884,2885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37267358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Nannan</creatorcontrib><creatorcontrib>Zhang, Yunpeng</creatorcontrib><creatorcontrib>Rivera-Rodriguez, Emmanuel J</creatorcontrib><creatorcontrib>Yu, Albert D</creatorcontrib><creatorcontrib>Hobin, Michael</creatorcontrib><creatorcontrib>Rosbash, Michael</creatorcontrib><creatorcontrib>Griffith, Leslie C</creatorcontrib><title>Widespread posttranscriptional regulation of cotransmission</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in
. We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a "translation-trap" strategy, we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of cotransmission is actively modulated. 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To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in
. We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a "translation-trap" strategy, we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of cotransmission is actively modulated. Posttranscriptional restriction of fast transmitter cotransmission provides a mechanism allowing reversible tuning of neuronal output.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>37267358</pmid><doi>10.1126/SCIADV.ADG9836</doi><orcidid>https://orcid.org/0000-0002-4899-525X</orcidid><orcidid>https://orcid.org/0000-0003-3164-9876</orcidid><orcidid>https://orcid.org/0000-0003-3366-1780</orcidid><orcidid>https://orcid.org/0000-0001-7805-9668</orcidid><orcidid>https://orcid.org/0009-0009-1919-3336</orcidid><orcidid>https://orcid.org/0000-0001-6014-0193</orcidid><orcidid>https://orcid.org/0000-0002-3483-6186</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Cellular Neuroscience Cholinergic Agents MicroRNAs - genetics MicroRNAs - metabolism Neurons - metabolism Neuroscience SciAdv r-articles Sleep - physiology Synaptic Transmission - genetics |
title | Widespread posttranscriptional regulation of cotransmission |
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