scholarly journals Minireview: Posttranscriptional Regulation of the Insulin and Insulin-Like Growth Factor Systems

Endocrinology ◽  
2009 ◽  
Vol 151 (4) ◽  
pp. 1403-1408 ◽  
Author(s):  
Eun Kyung Lee ◽  
Myriam Gorospe
Keyword(s):  
Glucose Homeostasis ◽  
Posttranscriptional Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Glucose Levels ◽  
Igf Receptors ◽  
The Stability ◽  
Mrna Binding

Insulin and IGFs share structural similarities and regulate metabolic processes including glucose homeostasis. Acute alterations in glucose levels trigger rapid changes in insulin concentration and insulin signaling. These processes are tightly regulated by posttranscriptional mechanisms that alter the stability and translation of mRNAs encoding insulin and the insulin receptor. Long-term glucose homeostasis is also modulated by IGFs and IGF receptors, whose expression is likewise subject to changes in the stability and translation of the encoding mRNAs. The control of mRNA half-life and translation is governed by RNA-binding proteins and microRNAs that interact with target transcripts at the 3′ and 5′ untranslated regions. In this review, we describe the RNA-binding proteins and microRNAs that target the mRNAs encoding insulin, IGFs, and their receptors. We discuss how these mRNA-binding factors help to elicit timely, versatile, and tissue-specific changes in insulin and IGF function, thereby effecting critical control of energy metabolism.

scholarly journals RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

2020 ◽  
Vol 21 (8) ◽  
pp. 2969 ◽  
Author(s):  
Katharina Jonas ◽  
George A. Calin ◽  
Martin Pichler
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Stability ◽  
Protein Coding ◽  
Cellular Processes ◽  
Open Questions ◽  
Non Coding Rnas ◽  
The Stability ◽  
Mrna Binding

The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. An important regulatory mechanism of lncRNAs is the post-transcriptional regulation mediated by RNA-binding proteins (RBPs). So far, however, only a small number of known cancer-associated lncRNAs have been found to be regulated by the interaction with RBPs like human antigen R (HuR), ARE/poly(U)-binding/degradation factor 1 (AUF1), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and tristetraprolin (TTP). These RBPs regulate, by various means, two aspects in particular, namely the stability and the localization of lncRNAs. Importantly, these RBPs themselves are commonly deregulated in cancer and might thus play a major role in the deregulation of cancer-related lncRNAs. There are, however, still many open questions, for example regarding the context specificity of these regulatory mechanisms that, in part, is based on the synergistic or competitive interaction between different RBPs. There is also a lack of knowledge on how RBPs facilitate the transport of lncRNAs between different cellular compartments.

scholarly journals Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins

2018 ◽  
Vol 81 ◽  
pp. 129-140 ◽  
Author(s):  
Abhishek K. Singh ◽  
Binod Aryal ◽  
Xinbo Zhang ◽  
Yuhua Fan ◽  
Nathan L. Price ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Posttranscriptional Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Non Coding Rnas

scholarly journals The endoplasmic reticulum-associated mRNA-binding proteins ERBP1 and ERBP2 interact in bloodstream-form Trypanosoma brucei

2019 ◽  
Author(s):  
Kathrin Bajak ◽  
Kevin Leiss ◽  
Christine Clayton ◽  
Esteban Erben
Keyword(s):  
Endoplasmic Reticulum ◽  
Ribosomal Protein ◽  
Trypanosoma Brucei ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Bloodstream Form ◽  
Control Of Gene Expression ◽  
Mrna Binding Proteins ◽  
Mrna Binding

AbstractKinetoplastids rely heavily on post-transcriptional mechanisms for control of gene expression, and on RNA-binding proteins that regulate mRNA splicing, translation and decay. Trypanosoma brucei ERBP1 (Tb927.10.14150) and ERBP2 (Tb927.9.9550) were previously identified as mRNA binding proteins that lack canonical RNA-binding domains. We here show that ERBP1 is associated with the endoplasmic reticulum, like ERBP2, and that the two proteins interact in vivo. Loss of ERBP1 from bloodstream-form T. brucei initially resulted in a growth defect but proliferation was restored after more prolonged cultivation. Results from a pull-down of tagged ERBP1 suggest that it preferentially binds to ribosomal protein mRNAs. The ERBP1 sequence resembles that of Saccharomyces cerevisiae Bfr1, which also localises to the endoplasmic reticulum and binds to ribosomal protein mRNAs. However, unlike Bfr1, ERBP1 does not bind to mRNAs encoding secreted proteins, and it is also not recruited to stress granules after starvation.

scholarly journals Control of Cytokine mRNA Expression by RNA-binding Proteins and microRNAs

2012 ◽  
Vol 91 (7) ◽  
pp. 651-658 ◽  
Author(s):  
V. Palanisamy ◽  
A. Jakymiw ◽  
E.A. Van Tubergen ◽  
N.J. D’Silva ◽  
K.L. Kirkwood
Keyword(s):  
Cancer Progression ◽  
Mrna Stability ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Periodontal Diseases ◽  
Pharyngeal Cancer ◽  
Cytokine Mrna ◽  
Mediators Of Inflammation ◽  
The Stability

Cytokines are critical mediators of inflammation and host defenses. Regulation of cytokines can occur at various stages of gene expression, including transcription, mRNA export, and post- transcriptional and translational levels. Among these modes of regulation, post-transcriptional regulation has been shown to play a vital role in controlling the expression of cytokines by modulating mRNA stability. The stability of cytokine mRNAs, including TNFα, IL-6, and IL-8, has been reported to be altered by the presence of AU-rich elements (AREs) located in the 3′-untranslated regions (3′UTRs) of the mRNAs. Numerous RNA-binding proteins and microRNAs bind to these 3′UTRs to regulate the stability and/or translation of the mRNAs. Thus, this paper describes the cooperative function between RNA-binding proteins and miRNAs and how they regulate AU-rich elements containing cytokine mRNA stability/degradation and translation. These mRNA control mechanisms can potentially influence inflammation as it relates to oral biology, including periodontal diseases and oral pharyngeal cancer progression.

Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains

2013 ◽  
Vol 394 (8) ◽  
pp. 1077-1090 ◽  
Author(s):  
Kristin Wächter ◽  
Marcel Köhn ◽  
Nadine Stöhr ◽  
Stefan Hüttelmaier
Keyword(s):  
Subcellular Localization ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Accumulation ◽  
Structural Constraints ◽  
Cellular Functions ◽  
Dependent Protein ◽  
Mrna Binding

Abstract The IGF2 mRNA-binding protein family (IGF2BPs) directs the cytoplasmic fate of various target mRNAs and controls essential cellular functions. The three IGF2BP paralogues expressed in mammals comprise two RNA-recognition motifs (RRM) as well as four KH domains. How these domains direct IGF2BP paralogue-dependent protein function remains largely elusive. In this study, we analyze the role of KH domains in IGF2BPs by the mutational GXXG-GEEG conversion of single KH domain loops in the context of full-length polypeptides. These analyses reveal that all four KH domains of IGF2BP1 and IGF2BP2 are essentially involved in RNA-binding in vitro and the cellular association with RNA-binding proteins (RBPs). Moreover the KH domains prevent the nuclear accumulation of these two paralogues and facilitate their recruitment to stress granules. The role of KH domains appears less pronounced in IGF2BP3, because GxxG-GEEG conversion in all four KH domains only modestly affects RNA-binding, subcellular localization and RNA-dependent protein association of this paralogue. These findings indicate paralogue-dependent RNA-binding properties of IGF2BPs which likely direct distinct cellular functions. Our findings suggest that IGF2BPs contact target RNAs via all four KH domains. This implies significant structural constraints, which presumably allow the formation of exceedingly stable protein-RNA complexes.

scholarly journals An Interaction between Two RNA Binding Proteins, Nab2 and Pub1, Links mRNA Processing/Export and mRNA Stability

2007 ◽  
Vol 27 (18) ◽  
pp. 6569-6579 ◽  
Author(s):  
Luciano H. Apponi ◽  
Seth M. Kelly ◽  
Michelle T. Harreman ◽  
Alexander N. Lehner ◽  
Anita H. Corbett ◽  
...  
Keyword(s):  
Mrna Stability ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Tail Length ◽  
Functional Link ◽  
Mrna Binding Protein ◽  
Mrna Binding

ABSTRACT mRNA stability is modulated by elements in the mRNA transcript and their cognate RNA binding proteins. Poly(U) binding protein 1 (Pub1) is a cytoplasmic Saccharomyces cerevisiae mRNA binding protein that stabilizes transcripts containing AU-rich elements (AREs) or stabilizer elements (STEs). In a yeast two-hybrid screen, we identified nuclear poly(A) binding protein 2 (Nab2) as being a Pub1-interacting protein. Nab2 is an essential nucleocytoplasmic shuttling mRNA binding protein that regulates poly(A) tail length and mRNA export. The interaction between Pub1 and Nab2 was confirmed by copurification and in vitro binding assays. The interaction is mediated by the Nab2 zinc finger domain. Analysis of the functional link between these proteins reveals that Nab2, like Pub1, can modulate the stability of specific mRNA transcripts. The half-life of the RPS16B transcript, an ARE-like sequence-containing Pub1 target, is decreased in both nab2-1 and nab2-67 mutants. In contrast, GCN4, an STE-containing Pub1 target, is not affected. Similar results were obtained for other ARE- and STE-containing Pub1 target transcripts. Further analysis reveals that the ARE-like sequence is necessary for Nab2-mediated transcript stabilization. These results suggest that Nab2 functions together with Pub1 to modulate mRNA stability and strengthen a model where nuclear events are coupled to the control of mRNA turnover in the cytoplasm.

scholarly journals Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer

Reproduction ◽  
2005 ◽  
Vol 130 (2) ◽  
pp. 203-212 ◽  
Author(s):  
Niels A Hammer ◽  
Thomas v O Hansen ◽  
Anne Grete Byskov ◽  
Eva Rajpert-De Meyts ◽  
Marie Louise Grøndahl ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Translational Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Developmental Expression ◽  
Human Testis ◽  
Mrna Binding Proteins ◽  
Mrna Binding

Insulin-like growth factor-II mRNA-binding proteins 1, 2 and 3 (IMP1, IMP2 and IMP3) belong to a family of RNA-binding proteins implicated in mRNA localization, turnover and translational control. We examined their expression pattern during development of murine and human testis and ovaries. In the mouse, IMPs were expressed in male and female gonadal cells at embryonic day 12.5 (E12.5). From E16.5, IMP1 and IMP3 became restricted to the developing germ cells, whereas IMP2 expression persisted in the interstitial cells. In mature mouse and human ovaries, IMP1, IMP2 and IMP3 were detected in resting and growing oocytes and in the granulosa cells. In testis, IMP1 and IMP3 were found mainly in the spermatogonia, whereas IMP2 was expressed in the immature Leydig cells. Moreover, all three IMPs were detected in human semen. The developmental expression pattern of IMP1 and IMP3 in the human testis prompted us to examine their possible involvement in testicular neoplasia. IMPs were detected primarily in germ-cell neoplasms, including preinvasive testicular carcinoma in situ, classical and spermatocytic seminoma, and nonseminomas, with particularly high expression in undifferentiated embryonal carcinoma. The relative expression of IMP1, IMP2 and IMP3 varied among tumor types and only IMP1 was detected in all carcinoma in situ cells. Thus IMPs, and in particular IMP1, may be useful auxiliary markers of testicular neoplasia.

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