HELZ directly interacts with CCR4–NOT and causes decay of bound mRNAs

Hanet, Aoife; Räsch, Felix; Weber, Ramona; Ruscica, Vincenzo; Fauser, Maria; Raisch, Tobias; Kuzuoğlu-Öztürk, Duygu; Chang, Chung Te; Bhandari, Dipankar; Igreja, Cátia; Wohlbold, Lara

doi:10.26508/lsa.201900405

Cited by 18 publications

(13 citation statements)

References 98 publications

(144 reference statements)

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“…To confirm that 4E-T has additional interactions with the CCR4-NOT complex, we performed binding assays in DDX6-null HEK293T cells (Hanet et al 2019). In cells depleted of DDX6, SBP-V5-4E-T still interacted with HA-NOT1 (Supplemental Fig.…”

Section: The Mid Region Of 4e-t Interacts With Ccr4-notmentioning

confidence: 99%

4E-T-bound mRNAs are stored in a silenced and deadenylated form

et al. 2020

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Human 4E-T is an eIF4E-binding protein (4E-BP) present in processing (P)-bodies that represses translation and regulates decay of mRNAs destabilized by AU-rich elements and microRNAs (miRNAs). However, the underlying regulatory mechanisms are still unclear. Here, we show that upon mRNA binding 4E-T represses translation and promotes deadenylation via the recruitment of the CCR4-NOT deadenylase complex. The interaction with CCR4-NOT is mediated by previously uncharacterized sites in the middle region of 4E-T. Importantly, mRNA decapping and decay are inhibited by 4E-T and the deadenylated target is stored in a repressed form. Inhibition of mRNA decapping requires the interaction of 4E-T with the cap-binding proteins eIF4E/4EHP. We further show that regulation of decapping by 4E-T participates in mRNA repression by the miRNA effector protein TNRC6B and that 4E-T overexpression interferes with tristetraprolin (TTP)-and NOT1-mediated mRNA decay. Thus, we postulate that 4E-T modulates 5 ′-to-3 ′ decay by swapping the fate of a deadenylated mRNA from complete degradation to storage. Our results provide insight into the mechanism of mRNA storage that controls localized translation and mRNA stability in P-bodies.

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Section: The Mid Region Of 4e-t Interacts With Ccr4-notmentioning

confidence: 99%

4E-T-bound mRNAs are stored in a silenced and deadenylated form

et al. 2020

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“…INO80D can accelerate atherosclerotic aging and induce hypertension and cataracts [80]. HELZ is associated with various mRNA decay factors, regulating the expression of genes related to the development of the nervous system [81]. AGO4 is closely related to ovarian development in laying hens, and its mutation may induce ovarian cancer [82].…”

Section: Aging-related Hub Genes Were Identified By Wgcnamentioning

confidence: 99%

Transcriptomic Analysis of Laying Hens Revealed the Role of Aging-Related Genes during Forced Molting

Zhang

Chen

Wen

et al. 2021

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Molting in birds provides us with an ideal genetic model for understanding aging and rejuvenation since birds present younger characteristics for reproduction and appearance after molting. Forced molting (FM) by fasting in chickens causes aging of their reproductive system and then promotes cell redevelopment by providing water and feed again. To reveal the genetic mechanism of rejuvenation, we detected blood hormone indexes and gene expression levels in the hypothalamus and ovary of hens from five different periods during FM. Three hormones were identified as participating in FM. Furthermore, the variation trends of gene expression levels in the hypothalamus and ovary at five different stages were found to be basically similar using transcriptome analysis. Among them, 45 genes were found to regulate cell aging during fasting stress and 12 genes were found to promote cell development during the recovery period in the hypothalamus. In addition, five hub genes (INO80D, HELZ, AGO4, ROCK2, and RFX7) were identified by WGCNA. FM can restart the reproductive function of aged hens by regulating expression levels of genes associated with aging and development. Our study not only enriches the theoretical basis of FM but also provides insights for the study of antiaging in humans and the conception mechanism in elderly women.

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“…Despite low expression, some of these proteins are compelling additions to the list of variably expressed proteins in skeletal muscles. While no activity in human skeletal muscles is known yet, HELZ was recently found to directly interact with the CCR4-NOT complex . Further, CNOT4 was shown to differentially express between skeletal muscles of two different sheep types .…”

Section: Resultsmentioning

confidence: 99%

“…While no activity in human skeletal muscles is known yet, HELZ was recently found to directly interact with the CCR4-NOT complex. 21 Further, CNOT4 was shown to differentially express between skeletal muscles of two different sheep types. 22 PITPNC1 was identified as variable between fast and slow avian myotubes in an expression array experiment but not further explored functionally in muscles.…”

Section: Cross Comparison Of Orthogonal Proteomic Datasetsmentioning

confidence: 96%

Spatial Proteomic Approach to Characterize Skeletal Muscle Myofibers

et al. 2020

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Skeletal muscle myofibers have differential protein expression resulting in functionally distinct slow- and fast-twitch types. While certain protein classes are well-characterized, the depth of all proteins involved in this process is unknown. We utilized the Human Protein Atlas (HPA) and the HPASubC tool to classify mosaic expression patterns of staining across 49,600 unique tissue microarray (TMA) images using a visual proteomic approach. We identified 2164 proteins with potential mosaic expression, of which 1605 were categorized as “likely” or “real.” This list included both well-known fiber-type-specific and novel proteins. A comparison of the 1605 mosaic proteins with a mass spectrometry (MS)-derived proteomic dataset of single human muscle fibers led to the assignment of 111 proteins to fiber types. We additionally used a multiplexed immunohistochemistry approach, a multiplexed RNA-ISH approach, and STRING v11 to further assign or suggest fiber types of newly characterized mosaic proteins. This visual proteomic analysis of mature skeletal muscle myofibers greatly expands the known repertoire of twitch-type-specific proteins.

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HELZ directly interacts with CCR4–NOT and causes decay of bound mRNAs

Cited by 18 publications

References 98 publications

4E-T-bound mRNAs are stored in a silenced and deadenylated form

4E-T-bound mRNAs are stored in a silenced and deadenylated form

Transcriptomic Analysis of Laying Hens Revealed the Role of Aging-Related Genes during Forced Molting

Spatial Proteomic Approach to Characterize Skeletal Muscle Myofibers

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