Roles of RNA-binding Proteins and Post-transcriptional Regulation in Driving Male Germ Cell Development in the Mouse

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved; however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA-binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation, or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSCs, its implications for normal, perturbed, and malignant hematopoiesis, and the most recent technological innovations aimed at RBP–RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

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Role of ELAV-like RNA-binding proteins HuD and HuR in the post-transcriptional regulation of acetylcholinesterase in neurons and skeletal muscle cells

Chemico-Biological Interactions ◽

10.1016/j.cbi.2005.10.004 ◽

2005 ◽

Vol 157-158 ◽

pp. 43-49 ◽

Cited By ~ 12

Author(s):

Julie Deschênes-Furry ◽

Lindsay M. Angus ◽

Guy Bélanger ◽

James Mwanjewe ◽

Bernard J. Jasmin

Keyword(s):

Skeletal Muscle ◽

Transcriptional Regulation ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Post Transcriptional Regulation

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Involvement of ELAV RNA-binding proteins in the post-transcriptional regulation of HO-1

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2014.00459 ◽

2015 ◽

Vol 8 ◽

Cited By ~ 4

Author(s):

Marialaura Amadio ◽

Giovanni Scapagnini ◽

Sergio Davinelli ◽

Vittorio Calabrese ◽

Stefano Govoni ◽

...

Keyword(s):

Transcriptional Regulation ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Post Transcriptional Regulation

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RNA-binding proteins involved in post-transcriptional regulation in bacteria

Frontiers in Microbiology ◽

10.3389/fmicb.2015.00141 ◽

2015 ◽

Vol 6 ◽

Cited By ~ 56

Author(s):

Elke Van Assche ◽

Sandra Van Puyvelde ◽

Jos Vanderleyden ◽

Hans P. Steenackers

Keyword(s):

Transcriptional Regulation ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Post Transcriptional Regulation

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The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects

Cancers ◽

10.3390/cancers12061539 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1539 ◽

Cited By ~ 2

Author(s):

Yogesh Saini ◽

Jian Chen ◽

Sonika Patial

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Zinc Finger ◽

Binding Proteins ◽

Rna Binding ◽

Zinc Finger Protein ◽

Rna Binding Proteins ◽

Regulation Of Gene Expression ◽

Finger Protein ◽

Post Transcriptional Regulation

Post-transcriptional regulation of gene expression plays a key role in cellular proliferation, differentiation, migration, and apoptosis. Increasing evidence suggests dysregulated post-transcriptional gene expression as an important mechanism in the pathogenesis of cancer. The tristetraprolin family of RNA-binding proteins (RBPs), which include Zinc Finger Protein 36 (ZFP36; commonly referred to as tristetraprolin (TTP)), Zinc Finger Protein 36 like 1 (ZFP36L1), and Zinc Finger Protein 36 like 2 (ZFP36L2), play key roles in the post-transcriptional regulation of gene expression. Mechanistically, these proteins function by binding to the AU-rich elements within the 3′-untranslated regions of their target mRNAs and, in turn, increasing mRNA turnover. The TTP family RBPs are emerging as key regulators of multiple biological processes relevant to cancer and are aberrantly expressed in numerous human cancers. The TTP family RBPs have tumor-suppressive properties and are also associated with cancer prognosis, metastasis, and resistance to chemotherapy. Herein, we summarize the various hallmark molecular traits of cancers that are reported to be regulated by the TTP family RBPs. We emphasize the role of the TTP family RBPs in the regulation of trait-associated mRNA targets in relevant cancer types/cell lines. Finally, we highlight the potential of the TTP family RBPs as prognostic indicators and discuss the possibility of targeting these TTP family RBPs for therapeutic benefits.

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nos-1 and nos-2, two genes related to Drosophila nanos, regulate primordial germ cell development and survival in Caenorhabditis elegans

Development ◽

10.1242/dev.126.21.4861 ◽

1999 ◽

Vol 126 (21) ◽

pp. 4861-4871 ◽

Cited By ~ 17

Author(s):

K. Subramaniam ◽

G. Seydoux

Keyword(s):

Caenorhabditis Elegans ◽

Germ Cell ◽

Rna Binding ◽

Rna Binding Proteins ◽

Primordial Germ Cell ◽

Gene Families ◽

Cell Development ◽

Embryonic Patterning ◽

Germ Cell Development ◽

C Elegans

In Drosophila, the posterior determinant nanos is required for embryonic patterning and for primordial germ cell (PGC) development. We have identified three genes in Caenorhabditis elegans that contain a putative zinc-binding domain similar to the one found in nanos, and show that two of these genes function during PGC development. Like Drosophila nanos, C. elegans nos-1 and nos-2 are not generally required for PGC fate specification, but instead regulate specific aspects of PGC development. nos-2 is expressed in PGCs around the time of gastrulation from a maternal RNA associated with P granules, and is required for the efficient incorporation of PGCs into the somatic gonad. nos-1 is expressed in PGCs after gastrulation, and is required redundantly with nos-2 to prevent PGCs from dividing in starved animals and to maintain germ cell viability during larval development. In the absence of nos-1 and nos-2, germ cells cease proliferation at the end of the second larval stage, and die in a manner that is partially dependent on the apoptosis gene ced-4. Our results also indicate that putative RNA-binding proteins related to Drosophila Pumilio are required for the same PGC processes as nos-1 and nos-2. These studies demonstrate that evolutionarily distant organisms utilize conserved factors to regulate early germ cell development and survival, and that these factors include members of the nanos and pumilio gene families.

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