Cargando…

YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1

YTH domain family 2 (YTHDF2) is an N6-methyladenosine (m(6)A) binding protein promoting mRNA degradation in various biological processes. Despite its essential roles, the role of YTHDF2 in determining cell fates has not been fully elucidated. Notch signaling plays a vital role in determining cell fa...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Byongsun, Lee, Seungjae, Shim, Jaekyung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495403/
https://www.ncbi.nlm.nih.gov/pubmed/34671198
http://dx.doi.org/10.7150/ijbs.61573
_version_ 1784579543502159872
author Lee, Byongsun
Lee, Seungjae
Shim, Jaekyung
author_facet Lee, Byongsun
Lee, Seungjae
Shim, Jaekyung
author_sort Lee, Byongsun
collection PubMed
description YTH domain family 2 (YTHDF2) is an N6-methyladenosine (m(6)A) binding protein promoting mRNA degradation in various biological processes. Despite its essential roles, the role of YTHDF2 in determining cell fates has not been fully elucidated. Notch signaling plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. We investigated the effect of YTHDF2 on Notch signaling. Our results show that YTHDF2 inhibits Notch signaling by downregulating the Notch1, HES1, and HES5 mRNA levels. Analyzing YTHDF2 deletion mutants indicates that the YTH domain is critical in regulating the Notch signal by directly binding m(6)A of Notch1 mRNA. Recently, YTHDF2 nuclear translocation was reported under heat shock conditions, but its physiological function is unknown. In our study, the YTH domain is required for YTHDF2 nuclear translocation. In addition, under heat shock stress, the Notch signal was significantly restored due to the increased expression of the Notch1 targets. These results suggest that YTHDF2 in the cytoplasm may act as an intrinsic suppressor in Notch signaling by promoting Notch1 mRNA degradation under normal cellular conditions. Conversely, upon the extracellular stress such as heat shock, YTHDF2 nuclear translocation resulting in reduced Notch1 mRNA decay may contribute to the increasing of Notch intracellular domain (NICD) regulating the survival-related target genes.
format Online
Article
Text
id pubmed-8495403
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-84954032021-10-19 YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1 Lee, Byongsun Lee, Seungjae Shim, Jaekyung Int J Biol Sci Research Paper YTH domain family 2 (YTHDF2) is an N6-methyladenosine (m(6)A) binding protein promoting mRNA degradation in various biological processes. Despite its essential roles, the role of YTHDF2 in determining cell fates has not been fully elucidated. Notch signaling plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. We investigated the effect of YTHDF2 on Notch signaling. Our results show that YTHDF2 inhibits Notch signaling by downregulating the Notch1, HES1, and HES5 mRNA levels. Analyzing YTHDF2 deletion mutants indicates that the YTH domain is critical in regulating the Notch signal by directly binding m(6)A of Notch1 mRNA. Recently, YTHDF2 nuclear translocation was reported under heat shock conditions, but its physiological function is unknown. In our study, the YTH domain is required for YTHDF2 nuclear translocation. In addition, under heat shock stress, the Notch signal was significantly restored due to the increased expression of the Notch1 targets. These results suggest that YTHDF2 in the cytoplasm may act as an intrinsic suppressor in Notch signaling by promoting Notch1 mRNA degradation under normal cellular conditions. Conversely, upon the extracellular stress such as heat shock, YTHDF2 nuclear translocation resulting in reduced Notch1 mRNA decay may contribute to the increasing of Notch intracellular domain (NICD) regulating the survival-related target genes. Ivyspring International Publisher 2021-08-28 /pmc/articles/PMC8495403/ /pubmed/34671198 http://dx.doi.org/10.7150/ijbs.61573 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Lee, Byongsun
Lee, Seungjae
Shim, Jaekyung
YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1
title YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1
title_full YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1
title_fullStr YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1
title_full_unstemmed YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1
title_short YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1
title_sort ythdf2 suppresses notch signaling through post-transcriptional regulation on notch1
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495403/
https://www.ncbi.nlm.nih.gov/pubmed/34671198
http://dx.doi.org/10.7150/ijbs.61573
work_keys_str_mv AT leebyongsun ythdf2suppressesnotchsignalingthroughposttranscriptionalregulationonnotch1
AT leeseungjae ythdf2suppressesnotchsignalingthroughposttranscriptionalregulationonnotch1
AT shimjaekyung ythdf2suppressesnotchsignalingthroughposttranscriptionalregulationonnotch1