TY - JOUR

T1 - EIF4A3

T2 - a gatekeeper of autophagy

AU - Sakellariou, Despoina

AU - Frankel, Lisa B.

N1 - Publisher Copyright: © 2021 Informa UK Limited, trading as Taylor & Francis Group.

PY - 2021

Y1 - 2021

N2 - EIF4A3 (eukaryotic translation initiation factor 4A3) is an RNA helicase and core component of the exon junction complex. While this RNA-binding protein (RBP) is well-characterized for its crucial roles in splicing, RNA trafficking and nonsense-mediated decay, its role in the regulation of metabolic signaling pathways remains elusive. In a recent study, we describe a new role for EIF4A3 as a negative regulator of macroautophagy/autophagy. Mechanistically, we report that EIF4A3, through its ability to safeguard splicing, can maintain low basal levels of autophagy through the cytosolic retention of the key autophagy transcription factor TFEB. Upon EIF4A3 depletion, the shuttling of TFEB to the nucleus results in an integrated transcriptional response, which induces both early and late steps of the autophagy pathway and enhances autophagic flux. We further report the upregulation of EIF4A3 across multiple cancer types and highlight the relevance of this newly identified EIF4A3-TFEB signaling axis in human tumors.

AB - EIF4A3 (eukaryotic translation initiation factor 4A3) is an RNA helicase and core component of the exon junction complex. While this RNA-binding protein (RBP) is well-characterized for its crucial roles in splicing, RNA trafficking and nonsense-mediated decay, its role in the regulation of metabolic signaling pathways remains elusive. In a recent study, we describe a new role for EIF4A3 as a negative regulator of macroautophagy/autophagy. Mechanistically, we report that EIF4A3, through its ability to safeguard splicing, can maintain low basal levels of autophagy through the cytosolic retention of the key autophagy transcription factor TFEB. Upon EIF4A3 depletion, the shuttling of TFEB to the nucleus results in an integrated transcriptional response, which induces both early and late steps of the autophagy pathway and enhances autophagic flux. We further report the upregulation of EIF4A3 across multiple cancer types and highlight the relevance of this newly identified EIF4A3-TFEB signaling axis in human tumors.

KW - Autophagy regulation

KW - cancer

KW - EIF4A3

KW - exon skipping

KW - GSK3B

KW - RNA-binding proteins

KW - TFEB

U2 - 10.1080/15548627.2021.1985881

DO - 10.1080/15548627.2021.1985881

M3 - Journal article

C2 - 34643458

AN - SCOPUS:85117246013

VL - 17

SP - 4504

EP - 4505

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 12

ER -