Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation

During Drosophila and vertebrate brain development, the conserved transcription factor Prospero/Prox1 is an important regulator of the transition between proliferation and differentiation. Prospero level is low in neural stem cells and their immediate progeny, but is upregulated in larval neurons an...

詳細記述

書誌詳細
主要な著者: Samuels, TJ, Arava, Y, Järvelin, AI, Robertson, F, Lee, JY, Yang, L, Yang, C-P, Lee, T, Ish-Horowicz, D, Davis, I
フォーマット: Journal article
言語:English
出版事項: Company of Biologists 2020
_version_ 1826305050642743296
author Samuels, TJ
Arava, Y
Järvelin, AI
Robertson, F
Lee, JY
Yang, L
Yang, C-P
Lee, T
Ish-Horowicz, D
Davis, I
author_facet Samuels, TJ
Arava, Y
Järvelin, AI
Robertson, F
Lee, JY
Yang, L
Yang, C-P
Lee, T
Ish-Horowicz, D
Davis, I
author_sort Samuels, TJ
collection OXFORD
description During Drosophila and vertebrate brain development, the conserved transcription factor Prospero/Prox1 is an important regulator of the transition between proliferation and differentiation. Prospero level is low in neural stem cells and their immediate progeny, but is upregulated in larval neurons and it is unknown how this process is controlled. Here, we use single molecule fluorescent in situ hybridisation to show that larval neurons selectively transcribe a long prospero mRNA isoform containing a 15 kb 3' untranslated region, which is bound in the brain by the conserved RNA-binding protein Syncrip/hnRNPQ. Syncrip binding increases the mRNA stability of the long prospero isoform, which allows an upregulation of Prospero protein production. Adult flies selectively lacking the long prospero isoform show abnormal behaviour that could result from impaired locomotor or neurological activity. Our findings highlight a regulatory strategy involving alternative polyadenylation followed by differential post-transcriptional regulation.
first_indexed 2024-03-07T06:26:58Z
format Journal article
id oxford-uuid:f4a3d0f0-1335-47ca-94bd-0008cf9e1ddb
institution University of Oxford
language English
last_indexed 2024-03-07T06:26:58Z
publishDate 2020
publisher Company of Biologists
record_format dspace
spelling oxford-uuid:f4a3d0f0-1335-47ca-94bd-0008cf9e1ddb2022-03-27T12:21:22ZNeuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f4a3d0f0-1335-47ca-94bd-0008cf9e1ddbEnglishSymplectic ElementsCompany of Biologists2020Samuels, TJArava, YJärvelin, AIRobertson, FLee, JYYang, LYang, C-PLee, TIsh-Horowicz, DDavis, IDuring Drosophila and vertebrate brain development, the conserved transcription factor Prospero/Prox1 is an important regulator of the transition between proliferation and differentiation. Prospero level is low in neural stem cells and their immediate progeny, but is upregulated in larval neurons and it is unknown how this process is controlled. Here, we use single molecule fluorescent in situ hybridisation to show that larval neurons selectively transcribe a long prospero mRNA isoform containing a 15 kb 3' untranslated region, which is bound in the brain by the conserved RNA-binding protein Syncrip/hnRNPQ. Syncrip binding increases the mRNA stability of the long prospero isoform, which allows an upregulation of Prospero protein production. Adult flies selectively lacking the long prospero isoform show abnormal behaviour that could result from impaired locomotor or neurological activity. Our findings highlight a regulatory strategy involving alternative polyadenylation followed by differential post-transcriptional regulation.
spellingShingle Samuels, TJ
Arava, Y
Järvelin, AI
Robertson, F
Lee, JY
Yang, L
Yang, C-P
Lee, T
Ish-Horowicz, D
Davis, I
Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
title Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
title_full Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
title_fullStr Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
title_full_unstemmed Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
title_short Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
title_sort neuronal upregulation of prospero protein is driven by alternative mrna polyadenylation and syncrip mediated mrna stabilisation
work_keys_str_mv AT samuelstj neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation
AT aravay neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation
AT jarvelinai neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation
AT robertsonf neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation
AT leejy neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation
AT yangl neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation
AT yangcp neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation
AT leet neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation
AT ishhorowiczd neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation
AT davisi neuronalupregulationofprosperoproteinisdrivenbyalternativemrnapolyadenylationandsyncripmediatedmrnastabilisation