Special Issue "Translational Regulation of Biological Processes"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 5595

Special Issue Editor

Dr. Johannes Haybaeck
E-Mail Website
Guest Editor
1. Department of Neuropathology, Diagnostic & Research Center for Molecular BioMedicine, Institute of Pathology, Medical University of Graz, Graz, Austria
2. Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
3. Department of Pathology, Neuropathology, and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria
4. Center for Biomarker Research in Medicine, Graz, Austria; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany

Special Issue Information

Dear Colleagues,

A dysregulation of protein biosynthesis is now considered a hallmark of several diseases, including cancer. Changes in protein synthesis are a crucial factor in establishing the cellular proteome, hence controlling cell proliferation, differentiation, and development, and thus, the progression of aging, age-related diseases and cancer.

An important limiting factor for protein biosynthesis is the initiation of translation. This process comprises a highly organized sequence of interactions between the structural features of mRNA and eukaryotic translation initiation factors. These interactions are regulated by a number of molecular switches, often regulated by signaling pathways that are well-known drivers of carcinogenesis. Translation initiation factors do not only regulate translation in a quantitative manner but also influence qualitative changes in mRNA translation; recent evidence shows that they can even control mRNA splicing.

In this Special Issue, we would like to invite researchers to present studies on the dysregulation of translation initiation and other issues on translational control and its effects on carcinogenesis but also other biological processes. We particularly encourage the submission of original research papers dealing with, but not restricted to, the influence of translation on the molecular mechanisms of regulation and assembly of eukaryotic initiation factor–mRNA complexes and how this alters cellular physiology. Additionally, papers are invited providing evidence that translation initiation may represent a promising therapeutic target for therapy. We also welcome review articles describing our current knowledge of the regulation of translation and its role in physiologic and pathologic processes.

Prof. Dr. Johannes Haybaeck
Guest Editor

Manuscript Submission Information

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Published Papers (4 papers)

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Research

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Article
The Drosophila RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA Set
Cells 2020, 9(3), 550; https://doi.org/10.3390/cells9030550 - 26 Feb 2020
Cited by 1 | Viewed by 1453
Abstract
DDX3 subfamily DEAD-box RNA helicases are essential developmental regulators of RNA metabolism in eukaryotes. belle, the single DDX3 ortholog in Drosophila, is required for fly viability, fertility, and germline stem cell maintenance. Belle is involved both in translational activation and repression of [...] Read more.
DDX3 subfamily DEAD-box RNA helicases are essential developmental regulators of RNA metabolism in eukaryotes. belle, the single DDX3 ortholog in Drosophila, is required for fly viability, fertility, and germline stem cell maintenance. Belle is involved both in translational activation and repression of target mRNAs in different tissues; however, direct targets of Belle in the testes are essentially unknown. Here we showed that belle RNAi knockdown in testis cyst cells caused a disruption of adhesion between germ and cyst cells and generation of tumor-like clusters of stem-like germ cells. Ectopic expression of β-integrin in cyst cells rescued early stages of spermatogenesis in belle knockdown testes, indicating that integrin adhesion complexes are required for the interaction between somatic and germ cells in a cyst. To address Belle functions in spermatogenesis in detail we performed cross-linking immunoprecipitation and sequencing (CLIP-seq) analysis and identified multiple mRNAs that interacted with Belle in the testes. The set of Belle targets includes transcripts of proteins that are essential for preventing the tumor-like clusters of germ cells and for sustaining spermatogenesis. By our hypothesis, failures in the translation of a number of mRNA targets additively contribute to developmental defects observed in the testes with belle knockdowns both in cyst cells and in the germline. Full article
(This article belongs to the Special Issue Translational Regulation of Biological Processes)
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Article
Translation Efficiency and Degradation of ER-Associated mRNAs Modulated by ER-Anchored poly(A)-Specific Ribonuclease (PARN)
Cells 2020, 9(1), 162; https://doi.org/10.3390/cells9010162 - 09 Jan 2020
Cited by 4 | Viewed by 1663
Abstract
Translation is spatiotemporally regulated and endoplasmic reticulum (ER)-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, [...] Read more.
Translation is spatiotemporally regulated and endoplasmic reticulum (ER)-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues. Consistently, purified recombinant PARN exhibited a strong ability to insert into the Langmuir monolayer and liposome. ER-anchored PARN was found to be able to reshape the poly(A) length profile of the ER-associated RNAs by suppressing long poly(A) tails without significantly influencing the cytosolic RNAs. The shortening of long poly(A) tails did not affect global translation efficiency, which suggests that the non-specific action of PARN towards long poly(A) tails was beyond the scope of translation regulation on the ER surface. Transcriptome sequencing analysis indicated that the ER-anchored PARN trigged the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulated the translation of its targets by redistributing ribosomes to heavy polysomes, which suggests that PARN might play a role in dynamic ribosome reallocation. During DNA damage response, MK2 phosphorylated PARN-Ser557 to modulate PARN translocation from the ER to cytosol. The ER-anchored PARN modulated DNA damage response and thereby cell viability by promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy. These findings revealed that highly regulated communication between mRNA degradation rate and translation efficiency is present on the ER surface in situ and PARN might contribute to this communication by modulating the dynamic ribosome reallocation between transcripts with low and high ribosome occupancies. Full article
(This article belongs to the Special Issue Translational Regulation of Biological Processes)
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Review

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Review
2′O-Ribose Methylation of Ribosomal RNAs: Natural Diversity in Living Organisms, Biological Processes, and Diseases
Cells 2021, 10(8), 1948; https://doi.org/10.3390/cells10081948 - 31 Jul 2021
Cited by 2 | Viewed by 882
Abstract
Recent findings suggest that ribosomes, the translational machineries, can display a distinct composition depending on physio-pathological contexts. Thanks to outstanding technological breakthroughs, many studies have reported that variations of rRNA modifications, and more particularly the most abundant rRNA chemical modification, the rRNA 2′O-ribose [...] Read more.
Recent findings suggest that ribosomes, the translational machineries, can display a distinct composition depending on physio-pathological contexts. Thanks to outstanding technological breakthroughs, many studies have reported that variations of rRNA modifications, and more particularly the most abundant rRNA chemical modification, the rRNA 2′O-ribose methylation (2′Ome), intrinsically occur in many organisms. In the last 5 years, accumulating reports have illustrated that rRNA 2′Ome varies in human cell lines but also in living organisms (yeast, plant, zebrafish, mouse, human) during development and diseases. These rRNA 2′Ome variations occur either within a single cell line, organ, or patient’s sample (i.e., intra-variability) or between at least two biological conditions (i.e., inter-variability). Thus, the ribosomes can tolerate the absence of 2′Ome at some specific positions. These observations question whether variations in rRNA 2′Ome could provide ribosomes with particular translational regulatory activities and functional specializations. Here, we compile recent studies supporting the heterogeneity of ribosome composition at rRNA 2′Ome level and provide an overview of the natural diversity in rRNA 2′Ome that has been reported up to now throughout the kingdom of life. Moreover, we discuss the little evidence that suggests that variations of rRNA 2′Ome can effectively impact the ribosome activity and contribute to the etiology of some human diseases. Full article
(This article belongs to the Special Issue Translational Regulation of Biological Processes)
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Review
Role of Cyclin-Dependent Kinase 1 in Translational Regulation in the M-Phase
Cells 2020, 9(7), 1568; https://doi.org/10.3390/cells9071568 - 27 Jun 2020
Cited by 14 | Viewed by 1332
Abstract
Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for [...] Read more.
Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of CDK1 in the initiation and elongation steps of protein synthesis in the cell. During its activation, CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1 to optimize temporal synthesis of proteins to sustain the division-related processes: mitosis and cytokinesis. Full article
(This article belongs to the Special Issue Translational Regulation of Biological Processes)
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