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

被引:13
作者
Corral, Victor M. [1 ]
Schultz, Eric R. [1 ]
Eisenstein, Richard S. [2 ]
Connell, Gregory J. [1 ]
机构
[1] Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55455 USA
[2] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA
关键词
UNTRANSLATED REGION; DEPENDENT REGULATION; RESPONSIVE ELEMENTS; DEFICIENCY ANEMIA; STEM-LOOP; T-CELLS; ACTIVATION; EXPRESSION; PROTEIN; DECAY;
D O I
10.1016/j.isci.2021.102360
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 TfR1mRNA 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.
引用
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页数:20
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