The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells

Patrick Connerty; Sarah Bajan; Judit Remenyi; Frances Fuller-Pace; Gyorgy Hutvagner

doi:10.1016/j.bbagrm.2016.07.013

The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells

Patrick Connerty, Sarah Bajan, Judit Remenyi, Frances Fuller-Pace, Gyorgy Hutvagner (Lead / Corresponding author)

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Abstract

MicroRNAs (miRNAs) are short (21-23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors.

Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2.

Original language	English
Pages (from-to)	1299-1305
Number of pages	6
Journal	BBA - Gene Regulatory Mechanisms
Volume	1859
Issue number	10
Early online date	28 Jul 2016
DOIs	https://doi.org/10.1016/j.bbagrm.2016.07.013
Publication status	Published - Oct 2016

Keywords

miRNA
p72
DDX17
KHSRP
Argonaute

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10.1016/j.bbagrm.2016.07.013

Author Accepted ManuscriptAccepted author manuscript, 588 KBLicence: CC BY-NC-ND

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title = "The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells",

abstract = "MicroRNAs (miRNAs) are short (21-23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors.Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2.",

keywords = "miRNA, p72, DDX17, KHSRP, Argonaute",

author = "Patrick Connerty and Sarah Bajan and Judit Remenyi and Frances Fuller-Pace and Gyorgy Hutvagner",

note = "G.H. is an ARC Future Fellow and this work was supported by the Australian Research Council Future Fellowship (FT110100455). J.R. was funded by a grant from Breast Cancer Now (2010NOVPR16) (previously known as Breast Cancer Campaign).",

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T1 - The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells

AU - Connerty, Patrick

AU - Bajan, Sarah

AU - Remenyi, Judit

AU - Fuller-Pace, Frances

AU - Hutvagner, Gyorgy

N1 - G.H. is an ARC Future Fellow and this work was supported by the Australian Research Council Future Fellowship (FT110100455). J.R. was funded by a grant from Breast Cancer Now (2010NOVPR16) (previously known as Breast Cancer Campaign).

PY - 2016/10

Y1 - 2016/10

N2 - MicroRNAs (miRNAs) are short (21-23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors.Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2.

AB - MicroRNAs (miRNAs) are short (21-23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors.Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2.

KW - miRNA

KW - p72

KW - DDX17

KW - KHSRP

KW - Argonaute

U2 - 10.1016/j.bbagrm.2016.07.013

DO - 10.1016/j.bbagrm.2016.07.013

M3 - Article

SN - 1874-9399

VL - 1859

SP - 1299

EP - 1305

JO - BBA - Gene Regulatory Mechanisms

JF - BBA - Gene Regulatory Mechanisms

IS - 10

ER -

The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells

Abstract

Keywords

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