Evidence map›Paper›PMID 38836349›Full record

ArticleCirculation2024

IRE1α Mediates the Hypertrophic Growth of Cardiomyocytes Through Facilitating the Formation of Initiation Complex to Promote the Translation of TOP-Motif Transcripts.

Chao Li, Shiqian Li, Guangyu Zhang, Qinfeng Li, Weidan Song, Xiaoding Wang, Jane A Cook, Miesje van der Stoel, Bradley W Wright, Francisco Altamirano and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Chao LiDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-2060-4835
Shiqian LiDepartment of Anatomy and Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Finland (S.L., M.v.d.S., E.I.).ORCID 0000-0003-1663-0704
Guangyu ZhangDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0001-8145-6701
Qinfeng LiDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0003-0582-2102
Weidan SongDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0003-1254-418X
Xiaoding WangDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Jane A CookDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0009-0009-7364-6260
Miesje van der StoelDepartment of Anatomy and Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Finland (S.L., M.v.d.S., E.I.).ORCID 0000-0003-4245-2497
Bradley W WrightLaboratory of Functional Genomics and Translational Control, Cecil H. and Ida Green Center for Reproductive Biology Sciences (B.W.W., J.C.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-6233-831X
Francisco AltamiranoDepartment of Cardiovascular Sciences, Houston Methodist Research Institute, TX (F.A.).ORCID 0000-0002-1612-2729
Erica L NiewoldDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA (E.L.N., P.Z., Y.D., Z.V.W.).ORCID 0000-0001-6394-5085
Jungsoo HanDepartment of Molecular Biology (J.H., G.K., J.A.H.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-5066-0555
Garrett KimbleDepartment of Molecular Biology (J.H., G.K., J.A.H.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-1224-7241
Pengfei ZhangDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA (E.L.N., P.Z., Y.D., Z.V.W.).
Xiang LuoDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-7647-6094
Hery UrraFacultad de Odontología y Ciencias de la Rehabilitación, Universidad San Sebastián, Bellavista, Santiago, Chile (H.U.).
Herman I MayDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-9264-2320
Anwarul FerdousDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-9285-7719
Xue-Nan SunTouchstone Diabetes Center, Department of Internal Medicine (C.L., J.A.C., X.-N.S., P.E.S.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0003-2588-6648
Yingfeng DengDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA (E.L.N., P.Z., Y.D., Z.V.W.).
Elina IkonenDepartment of Anatomy and Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Finland (S.L., M.v.d.S., E.I.).
Claudio HetzCenter for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile (C.H.).ORCID 0000-0003-1120-7966
Randal J KaufmanDegenerative Diseases Program, Center for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (R.J.K.).ORCID 0000-0003-4277-316X
Kezhong ZhangCenter for Molecular Medicine and Genetics, Wayne State University, Detroit, MI (K.Z.).ORCID 0000-0002-6062-235X
Thomas G GilletteDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-7617-3544
Philipp E SchererTouchstone Diabetes Center, Department of Internal Medicine (C.L., J.A.C., X.-N.S., P.E.S.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0003-0680-3392
Joseph A HillDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-5379-1614
Jin ChenLaboratory of Functional Genomics and Translational Control, Cecil H. and Ida Green Center for Reproductive Biology Sciences (B.W.W., J.C.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-6634-4397
Zhao V WangDivision of Cardiology, Department of Internal Medicine (C.L., G.Z., Q.L., W.S., X.W., J.A.C., X.L., H.I.M., A.F., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-9904-9538

Funding

UT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Jeffrey M Zigman · 2022 to 2026
$7.4M
Role of the Xbp1s/GFAT1 axis in pathological cardiac remodellingR01HL137723 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI WANG, ZHAO · 2017 to 2025
$4.3M
Homeostatic Role of IRE1a-XBP1-PDI1 in Hepatic Lipid MetabolismR01DK103185 · NIDDK · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI KAUFMAN, RANDAL J. · 2015 to 2019
$2.9M
Cardiomyocyte bromodomain protein 4 (BRD4) in physiology and diseaseR01HL147933 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2020 to 2023
$2.5M
Mechanism of ER Protein Misfolding-Induced Mitochondrial DysfunctionR01DK113171 · NIDDK · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI KAUFMAN, RANDAL J. · 2017 to 2020
$2.5M
NHLBI NIH HHS R01 HL137723NHLBI NIH HHS R01 HL147933NIDDK NIH HHS P30 DK127984NIDDK NIH HHS R01 DK103185NIDDK NIH HHS R01 DK113171
6 · The paper itself

Abstract

backgroundCardiomyocyte growth is coupled with active protein synthesis, which is one of the basic biological processes in living cells. However, it is unclear whether the unfolded protein response transducers and effectors directly take part in the control of protein synthesis. The connection between critical functions of the unfolded protein response in cellular physiology and requirements of multiple processes for cell growth prompted us to investigate the role of the unfolded protein response in cell growth and underlying molecular mechanisms.

methodsCardiomyocyte-specific inositol-requiring enzyme 1α (IRE1α) knockout and overexpression mouse models were generated to explore its function in vivo. Neonatal rat ventricular myocytes were isolated and cultured to evaluate the role of IRE1α in cardiomyocyte growth in vitro. Mass spectrometry was conducted to identify novel interacting proteins of IRE1α. Ribosome sequencing and polysome profiling were performed to determine the molecular basis for the function of IRE1α in translational control.

resultsWe show that IRE1α is required for cell growth in neonatal rat ventricular myocytes under prohypertrophy treatment and in HEK293 cells in response to serum stimulation. At the molecular level, IRE1α directly interacts with eIF4G and eIF3, 2 critical components of the translation initiation complex. We demonstrate that IRE1α facilitates the formation of the translation initiation complex around the endoplasmic reticulum and preferentially initiates the translation of transcripts with 5' terminal oligopyrimidine motifs. We then reveal that IRE1α plays an important role in determining the selectivity and translation of these transcripts. We next show that IRE1α stimulates the translation of epidermal growth factor receptor through an unannotated terminal oligopyrimidine motif in its 5' untranslated region. We further demonstrate a physiological role of IRE1α-governed protein translation by showing that IRE1α is essential for cardiomyocyte growth and cardiac functional maintenance under hemodynamic stress in vivo.

conclusionsThese studies suggest a noncanonical, essential role of IRE1α in orchestrating protein synthesis, which may have important implications in cardiac hypertrophy in response to pressure overload and general cell growth under other physiological and pathological conditions.

Indexed as

EndoribonucleasesMyocytes, CardiacProtein Serine-Threonine KinasesAnimalsAnimals, NewbornCardiomegalyCells, CulturedEukaryotic Initiation Factor-4GHEK293 CellsHumansMiceMice, KnockoutMultienzyme ComplexesProtein BiosynthesisRatsRats, Sprague-DawleyEndoribonucleasesErn1 protein, mouseErn1 protein, ratEukaryotic Initiation Factor-4GMultienzyme ComplexesProtein Serine-Threonine KinasesEGFR proteineukaryonic initiation factorheart failureunfolded protein response

Identifiers

PMID38836349
PMCPMC11427172

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.