A STAT3 protein complex required for mitochondrial mRNA stability and cancer

C. Dilanka Fernando; W. Samantha N. Jayasekara; Chaitanya Inampudi; Maija R. J. Kohonen-Corish; Wendy A. Cooper; Traude H. Beilharz; Tracy M. Josephs; Daniel J. Garama; Daniel J. Gough

doi:10.1016/j.celrep.2023.113033

A STAT3 protein complex required for mitochondrial mRNA stability and cancer

C. Dilanka Fernando, W. Samantha N. Jayasekara, Chaitanya Inampudi, Maija R. J. Kohonen-Corish, Wendy A. Cooper, Traude H. Beilharz, Tracy M. Josephs, Daniel J. Garama, Daniel J. Gough

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

59 Downloads (Pure)

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3.

Original language	English
Article number	113033
Pages (from-to)	1-14
Number of pages	15
Journal	Cell Reports
Volume	42
Issue number	9
Early online date	12 Sept 2023
DOIs	https://doi.org/10.1016/j.celrep.2023.113033
Publication status	Published - 26 Sept 2023
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

CP: Cancer
CP: Molecular biology
LRPPRC
lung adenocarcinoma
mitochondria
mRNA stability
SLIRP
STAT3

Access to Document

10.1016/j.celrep.2023.113033Licence: CC BY-NC-ND

Publisher version (open access)Final published version, 4.09 MBLicence: CC BY-NC-ND

Cite this

@article{74543f737d68430eac98157e8859c611,

title = "A STAT3 protein complex required for mitochondrial mRNA stability and cancer",

abstract = "Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3.",

keywords = "CP: Cancer, CP: Molecular biology, LRPPRC, lung adenocarcinoma, mitochondria, mRNA stability, SLIRP, STAT3",

author = "Fernando, {C. Dilanka} and Jayasekara, {W. Samantha N.} and Chaitanya Inampudi and Kohonen-Corish, {Maija R. J.} and Cooper, {Wendy A.} and Beilharz, {Traude H.} and Josephs, {Tracy M.} and Garama, {Daniel J.} and Gough, {Daniel J.}",

note = "Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2023",

month = sep,

day = "26",

doi = "10.1016/j.celrep.2023.113033",

language = "English",

volume = "42",

pages = "1--14",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "9",

}

TY - JOUR

T1 - A STAT3 protein complex required for mitochondrial mRNA stability and cancer

AU - Fernando, C. Dilanka

AU - Jayasekara, W. Samantha N.

AU - Inampudi, Chaitanya

AU - Kohonen-Corish, Maija R. J.

AU - Cooper, Wendy A.

AU - Beilharz, Traude H.

AU - Josephs, Tracy M.

AU - Garama, Daniel J.

AU - Gough, Daniel J.

N1 - Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2023/9/26

Y1 - 2023/9/26

N2 - Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3.

AB - Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3.

KW - CP: Cancer

KW - CP: Molecular biology

KW - LRPPRC

KW - lung adenocarcinoma

KW - mitochondria

KW - mRNA stability

KW - SLIRP

KW - STAT3

UR - http://www.scopus.com/inward/record.url?scp=85170673035&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2023.113033

DO - 10.1016/j.celrep.2023.113033

M3 - Article

C2 - 37703176

SN - 2211-1247

VL - 42

SP - 1

EP - 14

JO - Cell Reports

JF - Cell Reports

IS - 9

M1 - 113033

ER -

A STAT3 protein complex required for mitochondrial mRNA stability and cancer

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this