Post-Transcriptional Control in the Regulation of Polyhydroxyalkanoates Synthesis

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated with their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic, and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure.

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C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent nuclear accumulation of Staufen in neurons

Human Molecular Genetics ◽

10.1093/hmg/ddab089 ◽

2021 ◽

Author(s):

Eun Seon Kim ◽

Chang Geon Chung ◽

Jeong Hyang Park ◽

Byung Su Ko ◽

Sung Soon Park ◽

...

Keyword(s):

Retinal Degeneration ◽

Rna Binding ◽

Rna Binding Proteins ◽

Nuclear Accumulation ◽

Heterozygous Mutation ◽

Pathological Feature ◽

Dependent Manner ◽

Cellular Processes ◽

Drosophila Model ◽

Post Transcriptional Regulation

Abstract RNA-binding proteins (RBPs) play essential roles in diverse cellular processes through post-transcriptional regulation of RNAs. The subcellular localization of RBPs is thus under tight control, the breakdown of which is associated with aberrant cytoplasmic accumulation of nuclear RBPs such as TDP-43 and FUS, well-known pathological markers for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). Here, we report in Drosophila model for ALS/FTD that nuclear accumulation of a cytoplasmic RBP, Staufen, may be a new pathological feature. We found that in Drosophila C4da neurons expressing PR36, one of the arginine-rich dipeptide repeat proteins (DPRs), Staufen accumulated in the nucleus in Importin- and RNA-dependent manner. Notably, expressing Staufen with exogenous NLS—but not with mutated endogenous NLS—potentiated PR-induced dendritic defect, suggesting that nuclear-accumulated Staufen can enhance PR toxicity. PR36 expression increased Fibrillarin staining in the nucleolus, which was enhanced by heterozygous mutation of stau (stau+/−), a gene that codes Staufen. Furthermore, knockdown of fib, which codes Fibrillarin, exacerbated retinal degeneration mediated by PR toxicity, suggesting that increased amount of Fibrillarin by stau+/− is protective. Stau+/− also reduced the amount of PR-induced nuclear-accumulated Staufen and mitigated retinal degeneration and rescued viability of flies expressing PR36. Taken together, our data show that nuclear accumulation of Staufen in neurons may be an important pathological feature contributing to the pathogenesis of ALS/FTD.

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Competing Endogenous RNAs in Cervical Carcinogenesis: A New Layer of Complexity

Processes ◽

10.3390/pr9060991 ◽

2021 ◽

Vol 9 (6) ◽

pp. 991

Author(s):

Fernanda Costa Brandão Berti ◽

Sara Cristina Lobo-Alves ◽

Camila de Freitas Oliveira-Toré ◽

Amanda Salviano-Silva ◽

Karen Brajão de Oliveira ◽

...

Keyword(s):

Gene Expression ◽

Fine Tuning ◽

Molecular Networks ◽

Cervical Carcinogenesis ◽

Molecular Changes ◽

Cellular Processes ◽

Target Mrnas ◽

Competing Endogenous Rnas ◽

Cervical Cells ◽

Post Transcriptional Regulation

MicroRNAs (miRNAs) regulate gene expression by binding to complementary sequences within target mRNAs. Apart from working ‘solo’, miRNAs may interact in important molecular networks such as competing endogenous RNA (ceRNA) axes. By competing for a limited pool of miRNAs, transcripts such as long noncoding RNAs (lncRNAs) and mRNAs can regulate each other, fine-tuning gene expression. Several ceRNA networks led by different lncRNAs—described here as lncRNA-mediated ceRNAs—seem to play essential roles in cervical cancer (CC). By conducting an extensive search, we summarized networks involved in CC, highlighting the major impacts of such dynamic molecular changes over multiple cellular processes. Through the sponging of distinct miRNAs, some lncRNAs as HOTAIR, MALAT1, NEAT1, OIP5-AS1, and XIST trigger crucial molecular changes, ultimately increasing cell proliferation, migration, invasion, and inhibiting apoptosis. Likewise, several lncRNAs seem to be a sponge for important tumor-suppressive miRNAs (as miR-140-5p, miR-143-3p, miR-148a-3p, and miR-206), impairing such molecules from exerting a negative post-transcriptional regulation over target mRNAs. Curiously, some of the involved mRNAs code for important proteins such as PTEN, ROCK1, and MAPK1, known to modulate cell growth, proliferation, apoptosis, and adhesion in CC. Overall, we highlight important lncRNA-mediated functional interactions occurring in cervical cells and their closely related impact on cervical carcinogenesis.

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TFEB Signalling-Related MicroRNAs and Autophagy

Biomolecules ◽

10.3390/biom11070985 ◽

2021 ◽

Vol 11 (7) ◽

pp. 985

Author(s):

Davide Corà ◽

Federico Bussolino ◽

Gabriella Doronzo

Keyword(s):

Transcriptional Regulation ◽

Stress Factors ◽

Cellular Functions ◽

Post Translational Modifications ◽

Cellular Processes ◽

Factor Deficiency ◽

Transcription Factor Eb ◽

Important Regulator ◽

Response To Stress ◽

Post Transcriptional Regulation

The oncogenic Transcription Factor EB (TFEB), a member of MITF-TFE family, is known to be the most important regulator of the transcription of genes responsible for the control of lysosomal biogenesis and functions, autophagy, and vesicles flux. TFEB activation occurs in response to stress factors such as nutrient and growth factor deficiency, hypoxia, lysosomal stress, and mitochondrial damage. To reach the final functional status, TFEB is regulated in multimodal ways, including transcriptional rate, post-transcriptional regulation, and post-translational modifications. Post-transcriptional regulation is in part mediated by miRNAs. miRNAs have been linked to many cellular processes involved both in physiology and pathology, such as cell migration, proliferation, differentiation, and apoptosis. miRNAs also play a significant role in autophagy, which exerts a crucial role in cell behaviour during stress or survival responses. In particular, several miRNAs directly recognise TFEB transcript or indirectly regulate its function by targeting accessory molecules or enzymes involved in its post-translational modifications. Moreover, the transcriptional programs triggered by TFEB may be influenced by the miRNA-mediated regulation of TFEB targets. Finally, recent important studies indicate that the transcription of many miRNAs is regulated by TFEB itself. In this review, we describe the interplay between miRNAs with TFEB and focus on how these types of crosstalk affect TFEB activation and cellular functions.

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Transcriptional Control of Clostridium autoethanogenum using CRISPRi

Synthetic Biology ◽

10.1093/synbio/ysab008 ◽

2021 ◽

Author(s):

Nick Fackler ◽

James Heffernan ◽

Alex Juminaga ◽

Damien Doser ◽

Shilpa Nagaraju ◽

...

Keyword(s):

Transcriptional Repression ◽

Transcriptional Control ◽

Genome Engineering ◽

Low Cost ◽

Pathway Engineering ◽

Industrial Emissions ◽

Gas Fermentation ◽

Control Gene Expression ◽

Clostridium Autoethanogenum ◽

Commercial Process

Abstract Gas fermentation by Clostridium autoethanogenum is a commercial process for the sustainable biomanufacturing of fuels and valuable chemicals using abundant, low cost C1 feedstocks (CO and CO2) from sources such as inedible biomass, unsorted and non-recyclable municipal solid waste, and industrial emissions. Efforts towards pathway engineering and elucidation of gene function in this microbe have been limited by a lack of genetic tools to control gene expression and arduous genome engineering methods. To increase the pace of progress, here we developed an inducible CRISPR interference (CRISPRi) system for C. autoethanogenum and applied that system towards transcriptional repression of genes with ostensibly crucial functions in metabolism.

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Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression

Blood ◽

10.1182/blood-2011-08-371344 ◽

2012 ◽

Vol 119 (17) ◽

pp. 4034-4046 ◽

Cited By ~ 101

Author(s):

Giuseppe Zardo ◽

Alberto Ciolfi ◽

Laura Vian ◽

Linda M. Starnes ◽

Monia Billi ◽

...

Keyword(s):

Gene Expression ◽

Dna Sequences ◽

Transcriptional Control ◽

Transcriptional Level ◽

Seed Region ◽

Mrna Targets ◽

Epigenetic Events ◽

Evolutionarily Conserved ◽

Lineage Decision ◽

Chromatin Remodeling Complexes

Abstract Epigenetic modifications regulate developmental genes involved in stem cell identity and lineage choice. NFI-A is a posttranscriptional microRNA-223 (miR-223) target directing human hematopoietic progenitor lineage decision: NFI-A induction or silencing boosts erythropoiesis or granulopoiesis, respectively. Here we show that NFI-A promoter silencing, which allows granulopoiesis, is guaranteed by epigenetic events, including the resolution of opposing chromatin “bivalent domains,” hypermethylation, recruitment of polycomb (PcG)–RNAi complexes, and miR-223 promoter targeting activity. During granulopoiesis, miR-223 localizes inside the nucleus and targets the NFI-A promoter region containing PcGs binding sites and miR-223 complementary DNA sequences, evolutionarily conserved in mammalians. Remarkably, both the integrity of the PcGs-RNAi complex and DNA sequences matching the seed region of miR-223 are required to induce NFI-A transcriptional silencing. Moreover, ectopic miR-223 expression in human myeloid progenitors causes heterochromatic repression of NFI-A gene and channels granulopoiesis, whereas its stable knockdown produces the opposite effects. Our findings indicate that, besides the regulation of translation of mRNA targets, endogenous miRs can affect gene expression at the transcriptional level, functioning in a critical interface between chromatin remodeling complexes and the genome to direct fate lineage determination of hematopoietic progenitors.

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Two new isoforms of the human hepatoma-derived growth factor interact with components of the cytoskeleton

Biological Chemistry ◽

10.1515/hsz-2015-0273 ◽

2016 ◽

Vol 397 (5) ◽

pp. 417-436 ◽

Cited By ~ 3

Author(s):

Jessica Nüße ◽

Ursula Mirastschijski ◽

Mario Waespy ◽

Janina Oetjen ◽

Nadine Brandes ◽

...

Keyword(s):

Growth Factor ◽

Ribosome Biogenesis ◽

Transcriptional Control ◽

Splice Variants ◽

Retrograde Transport ◽

Interaction Patterns ◽

Cytoskeleton Organization ◽

Cellular Processes ◽

Messenger Ribonucleoprotein ◽

Transport Site

Abstract Hepatoma-derived growth factor (HDGF) is involved in diverse, apparently unrelated processes, such as cell proliferation, apoptosis, DNA-repair, transcriptional control, ribosome biogenesis and cell migration. Most of the interactions of HDGF with diverse molecules has been assigned to the hath region of HDGF. In this study we describe two previously unknown HDGF isoforms, HDGF-B and HDGF-C, generated via alternative splicing with structurally unrelated N-terminal regions of their hath region, which is clearly different from the well described isoform, HDGF-A. In silico modeling revealed striking differences near the PHWP motif, an essential part of the binding site for glycosaminoglycans and DNA/RNA. This observation prompted the hypothesis that these isoforms would have distinct interaction patterns with correspondingly diverse roles on cellular processes. Indeed, we discovered specific associations of HDGF-B and HDGF-C with cytoskeleton elements, such as tubulin and dynein, suggesting previously unknown functions of HDGF in retrograde transport, site directed localization and/or cytoskeleton organization. In contrast, the main isoform HDGF-A does not interact directly with the cytoskeleton, but via RNA with messenger ribonucleoprotein (mRNP) complexes. In summary, the discovery of HDGF splice variants with their discrete binding activities and subcellular distributions opened new avenues for understanding its biological function and importance.

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Quantitative Proteomics Reveals that GmENO2 Proteins Are Involved in Response to Phosphate Starvation in the Leaves of Glycine max L.

International Journal of Molecular Sciences ◽

10.3390/ijms22020920 ◽

2021 ◽

Vol 22 (2) ◽

pp. 920

Author(s):

Ling Cheng ◽

Wanling Min ◽

Man Li ◽

Lili Zhou ◽

Chuan-Chih Hsu ◽

...

Keyword(s):

Glycine Max ◽

Molecular Mechanisms ◽

Human Life ◽

Phosphate Starvation ◽

Limiting Factor ◽

Transcriptional Level ◽

Label Free ◽

Promoter Regions ◽

Glycine Max L ◽

Soybean Plants

Soybean (Glycine max L.) is a major crop providing important source for protein and oil for human life. Low phosphate (LP) availability is a critical limiting factor affecting soybean production. Soybean plants develop a series of strategies to adapt to phosphate (Pi) limitation condition. However, the underlying molecular mechanisms responsible for LP stress response remain largely unknown. Here, we performed a label-free quantification (LFQ) analysis of soybean leaves grown under low and high phosphate conditions. We identified 267 induced and 440 reduced differential proteins from phosphate-starved leaves. Almost a quarter of the LP decreased proteins are involved in translation processes, while the LP increased proteins are accumulated in chlorophyll biosynthetic and carbon metabolic processes. Among these induced proteins, an enolase protein, GmENO2a was found to be mostly induced protein. On the transcriptional level, GmENO2a and GmENO2b, but not GmENO2c or GmENO2d, were dramatically induced by phosphate starvation. Among 14 enolase genes, only GmENO2a and GmENO2b genes contain the P1BS motif in their promoter regions. Furthermore, GmENO2b was specifically induced in the GmPHR31 overexpressing soybean plants. Our findings provide molecular insights into how soybean plants tune basic carbon metabolic pathway to adapt to Pi deprivation through the ENO2 enzymes.

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The Distinctive Regulation of Cyanobacterial Glutamine Synthetase

Life ◽

10.3390/life8040052 ◽

2018 ◽

Vol 8 (4) ◽

pp. 52 ◽

Cited By ~ 10

Author(s):

Paul Bolay ◽

M. Muro-Pastor ◽

Francisco Florencio ◽

Stephan Klähn

Keyword(s):

Glutamine Synthetase ◽

Gene Expression Regulation ◽

Feedback Inhibition ◽

Current Knowledge ◽

Transcriptional Level ◽

Distinctive Features ◽

Small Proteins ◽

Regulatory Systems ◽

Covalent Modifications ◽

Post Transcriptional Regulation

Glutamine synthetase (GS) features prominently in bacterial nitrogen assimilation as it catalyzes the entry of bioavailable nitrogen in form of ammonium into cellular metabolism. The classic example, the comprehensively characterized GS of enterobacteria, is subject to exquisite regulation at multiple levels, among them gene expression regulation to control GS abundance, as well as feedback inhibition and covalent modifications to control enzyme activity. Intriguingly, the GS of the ecologically important clade of cyanobacteria features fundamentally different regulatory systems to those of most prokaryotes. These include the interaction with small proteins, the so-called inactivating factors (IFs) that inhibit GS linearly with their abundance. In addition to this protein interaction-based regulation of GS activity, cyanobacteria use alternative elements to control the synthesis of GS and IFs at the transcriptional level. Moreover, cyanobacteria evolved unique RNA-based regulatory mechanisms such as glutamine riboswitches to tightly tune IF abundance. In this review, we aim to outline the current knowledge on the distinctive features of the cyanobacterial GS encompassing the overall control of its activity, sensing the nitrogen status, transcriptional and post-transcriptional regulation, as well as strain-specific differences.

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The circulating miRNAs as diagnostic and prognostic markers

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-0838 ◽

2019 ◽

Vol 57 (7) ◽

pp. 932-953 ◽

Cited By ~ 11

Author(s):

Alessandro Terrinoni ◽

Cosimo Calabrese ◽

Daniela Basso ◽

Ada Aita ◽

Sabrina Caporali ◽

...

Keyword(s):

Biological Fluids ◽

Mature Mirnas ◽

Transcriptional Level ◽

Circulating Mirnas ◽

Rna Sequences ◽

Regulate Gene Expression ◽

Rna Translation ◽

Cellular Processes ◽

New Class ◽

Clinical Biomarkers

Abstract A large portion of the human genome transcribes RNA sequences that do not code for any proteins. The first of these sequences was identified in 1993, and the best known noncoding RNAs are microRNA (miRNAs). It is now fully established that miRNAs regulate approximately 30% of the known genes that codify proteins. miRNAs are involved in several biological processes, like cell proliferation, differentiation, apoptosis and metastatization. These RNA products regulate gene expression at the post-transcriptional level, modulating or inhibiting protein expression by interacting with specific sequences of mRNAs. Mature miRNAs can be detected in blood plasma, serum and also in a wide variety of biological fluids. They can be found associated with proteins, lipids as well as enclosed in exosome vesicles. We know that circulating miRNAs (C-miRNAs) can regulate several key cellular processes in tissues different from the production site. C-miRNAs behave as endogenous mediators of RNA translation, and an extraordinary knowledge on their function has been obtained in the last years. They can be secreted in different tissue cells and associated with specific pathological conditions. Significant evidence indicates that the initiation and progression of several pathologies are “highlighted” by the presence of specific C-miRNAs, underlining their potential diagnostic relevance as clinical biomarkers. Here we review the current literature on the possible use of this new class of molecules as clinical biomarkers of diseases.

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Aberrant Post-Transcriptional Regulation of Protein Expression in the Development of Chronic Obstructive Pulmonary Disease

International Journal of Molecular Sciences ◽

10.3390/ijms222111963 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11963

Author(s):

Noof Aloufi ◽

Aeshah Alluli ◽

David H. Eidelman ◽

Carolyn J. Baglole

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Transcriptional Regulation ◽

Pulmonary Disease ◽

Rna Binding ◽

Rna Binding Proteins ◽

Chronic Obstructive ◽

Respiratory Disorder ◽

Obstructive Pulmonary Disease ◽

Cellular Processes ◽

Post Transcriptional Regulation

Chronic obstructive pulmonary disease (COPD) is an incurable and prevalent respiratory disorder that is characterized by chronic inflammation and emphysema. COPD is primarily caused by cigarette smoke (CS). CS alters numerous cellular processes, including the post-transcriptional regulation of mRNAs. The identification of RNA-binding proteins (RBPs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as main factors engaged in the regulation of RNA biology opens the door to understanding their role in coordinating physiological cellular processes. Dysregulation of post-transcriptional regulation by foreign particles in CS may lead to the development of diseases such as COPD. Here we review current knowledge about post-transcriptional events that may be involved in the pathogenesis of COPD.

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