Roquin is a major mediator of iron-regulated changes to transferrin receptor-1 mRNA stability

Victor M. Corral; Eric R. Schultz; Richard S. Eisenstein; Gregory J. Connell

doi:10.1016/j.isci.2021.102360

Roquin is a major mediator of iron-regulated changes to transferrin receptor-1 mRNA stability

Victor M. Corral, Eric R. Schultz, Richard S. Eisenstein, Gregory J. Connell

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

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Abstract

Transferrin receptor-1 (TfR1) has essential iron transport and proposed signal transduction functions. Proper TfR1 regulation is a requirement for hematopoiesis, neurological development, and the homeostasis of tissues including the intestine and muscle, while dysregulation is associated with cancers and immunodeficiency. TfR1 mRNA degradation is highly regulated, but the identity of the degradation activity remains uncertain. Here, we show with gene knockouts and siRNA knockdowns that two Roquin paralogs are major mediators of iron-regulated changes to the steady-state TfR1 mRNA level within four different cell types (HAP1, HUVEC, L-M, and MEF). Roquin is demonstrated to destabilize the TfR1 mRNA, and its activity is fully dependent on three hairpin loops within the TfR1 mRNA 3′-UTR that are essential for iron-regulated instability. We further show in L-M cells that TfR1 mRNA degradation does not require ongoing translation, consistent with Roquin-mediated instability. We conclude that Roquin is a major effector of TfR1 mRNA abundance.

Original language	English (US)
Article number	102360
Journal	iScience
Volume	24
Issue number	4
DOIs	https://doi.org/10.1016/j.isci.2021.102360
State	Published - Apr 23 2021

Bibliographical note

Funding Information:
We thank O Takeuchi ( Kyoto University , Japan) for a Regnase-1 expression plasmid. This work was supported in part by a University of Minnesota Multicultural Summer Research Opportunities Program (MSROP) award to V.M.C., an Undergraduate Research Opportunities Program (UROP) award to E.R.S., and a Grant-in-Aid from the Office of the Vice President for Research to G.J.C. We also acknowledge the University of Minnesota Imaging Centers for use of the phosphor scanner.

Funding Information:
We thank O Takeuchi (Kyoto University, Japan) for a Regnase-1 expression plasmid. This work was supported in part by a University of Minnesota Multicultural Summer Research Opportunities Program (MSROP) award to V.M.C. an Undergraduate Research Opportunities Program (UROP) award to E.R.S. and a Grant-in-Aid from the Office of the Vice President for Research to G.J.C. We also acknowledge the University of Minnesota Imaging Centers for use of the phosphor scanner. V.M.C. E.R.S. and G.J.C. contributed to the conduction and design of the experiments as well as the writing of the paper. R.S.E. contributed to the design of the experiments and writing of the paper. The authors declare no competing interests.

Publisher Copyright:
© 2021 The Author(s)

Keywords

Biological Sciences
Cell Biology
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2021.102360

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title = "Roquin is a major mediator of iron-regulated changes to transferrin receptor-1 mRNA stability",

abstract = "Transferrin receptor-1 (TfR1) has essential iron transport and proposed signal transduction functions. Proper TfR1 regulation is a requirement for hematopoiesis, neurological development, and the homeostasis of tissues including the intestine and muscle, while dysregulation is associated with cancers and immunodeficiency. TfR1 mRNA degradation is highly regulated, but the identity of the degradation activity remains uncertain. Here, we show with gene knockouts and siRNA knockdowns that two Roquin paralogs are major mediators of iron-regulated changes to the steady-state TfR1 mRNA level within four different cell types (HAP1, HUVEC, L-M, and MEF). Roquin is demonstrated to destabilize the TfR1 mRNA, and its activity is fully dependent on three hairpin loops within the TfR1 mRNA 3′-UTR that are essential for iron-regulated instability. We further show in L-M cells that TfR1 mRNA degradation does not require ongoing translation, consistent with Roquin-mediated instability. We conclude that Roquin is a major effector of TfR1 mRNA abundance.",

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author = "Corral, {Victor M.} and Schultz, {Eric R.} and Eisenstein, {Richard S.} and Connell, {Gregory J.}",

note = "Funding Information: We thank O Takeuchi ( Kyoto University , Japan) for a Regnase-1 expression plasmid. This work was supported in part by a University of Minnesota Multicultural Summer Research Opportunities Program (MSROP) award to V.M.C., an Undergraduate Research Opportunities Program (UROP) award to E.R.S., and a Grant-in-Aid from the Office of the Vice President for Research to G.J.C. We also acknowledge the University of Minnesota Imaging Centers for use of the phosphor scanner. Funding Information: We thank O Takeuchi (Kyoto University, Japan) for a Regnase-1 expression plasmid. This work was supported in part by a University of Minnesota Multicultural Summer Research Opportunities Program (MSROP) award to V.M.C. an Undergraduate Research Opportunities Program (UROP) award to E.R.S. and a Grant-in-Aid from the Office of the Vice President for Research to G.J.C. We also acknowledge the University of Minnesota Imaging Centers for use of the phosphor scanner. V.M.C. E.R.S. and G.J.C. contributed to the conduction and design of the experiments as well as the writing of the paper. R.S.E. contributed to the design of the experiments and writing of the paper. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",

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doi = "10.1016/j.isci.2021.102360",

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AU - Eisenstein, Richard S.

AU - Connell, Gregory J.

N1 - Funding Information: We thank O Takeuchi ( Kyoto University , Japan) for a Regnase-1 expression plasmid. This work was supported in part by a University of Minnesota Multicultural Summer Research Opportunities Program (MSROP) award to V.M.C., an Undergraduate Research Opportunities Program (UROP) award to E.R.S., and a Grant-in-Aid from the Office of the Vice President for Research to G.J.C. We also acknowledge the University of Minnesota Imaging Centers for use of the phosphor scanner. Funding Information: We thank O Takeuchi (Kyoto University, Japan) for a Regnase-1 expression plasmid. This work was supported in part by a University of Minnesota Multicultural Summer Research Opportunities Program (MSROP) award to V.M.C. an Undergraduate Research Opportunities Program (UROP) award to E.R.S. and a Grant-in-Aid from the Office of the Vice President for Research to G.J.C. We also acknowledge the University of Minnesota Imaging Centers for use of the phosphor scanner. V.M.C. E.R.S. and G.J.C. contributed to the conduction and design of the experiments as well as the writing of the paper. R.S.E. contributed to the design of the experiments and writing of the paper. The authors declare no competing interests. Publisher Copyright: © 2021 The Author(s)

PY - 2021/4/23

Y1 - 2021/4/23

N2 - Transferrin receptor-1 (TfR1) has essential iron transport and proposed signal transduction functions. Proper TfR1 regulation is a requirement for hematopoiesis, neurological development, and the homeostasis of tissues including the intestine and muscle, while dysregulation is associated with cancers and immunodeficiency. TfR1 mRNA degradation is highly regulated, but the identity of the degradation activity remains uncertain. Here, we show with gene knockouts and siRNA knockdowns that two Roquin paralogs are major mediators of iron-regulated changes to the steady-state TfR1 mRNA level within four different cell types (HAP1, HUVEC, L-M, and MEF). Roquin is demonstrated to destabilize the TfR1 mRNA, and its activity is fully dependent on three hairpin loops within the TfR1 mRNA 3′-UTR that are essential for iron-regulated instability. We further show in L-M cells that TfR1 mRNA degradation does not require ongoing translation, consistent with Roquin-mediated instability. We conclude that Roquin is a major effector of TfR1 mRNA abundance.

AB - Transferrin receptor-1 (TfR1) has essential iron transport and proposed signal transduction functions. Proper TfR1 regulation is a requirement for hematopoiesis, neurological development, and the homeostasis of tissues including the intestine and muscle, while dysregulation is associated with cancers and immunodeficiency. TfR1 mRNA degradation is highly regulated, but the identity of the degradation activity remains uncertain. Here, we show with gene knockouts and siRNA knockdowns that two Roquin paralogs are major mediators of iron-regulated changes to the steady-state TfR1 mRNA level within four different cell types (HAP1, HUVEC, L-M, and MEF). Roquin is demonstrated to destabilize the TfR1 mRNA, and its activity is fully dependent on three hairpin loops within the TfR1 mRNA 3′-UTR that are essential for iron-regulated instability. We further show in L-M cells that TfR1 mRNA degradation does not require ongoing translation, consistent with Roquin-mediated instability. We conclude that Roquin is a major effector of TfR1 mRNA abundance.

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KW - Cell Biology

KW - Molecular Biology

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JO - iScience

JF - iScience

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ER -

Roquin is a major mediator of iron-regulated changes to transferrin receptor-1 mRNA stability

Abstract

Bibliographical note

Keywords

UN SDGs

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Roquin is a major mediator of iron-regulated changes to transferrin receptor-1 mRNA stability

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

Find It

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Fingerprint

University Assets

Typhoon FLA 9500

University Imaging Centers

Cite this