scholarly journals microRNAs Mediated Regulation of the Ribosomal Proteins and its Consequences on the Global Translation of Proteins

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 110
Author(s):  
Abu Musa Md Talimur Reza ◽  
Yu-Guo Yuan
Keyword(s):  
Gene Expression ◽  
Untranslated Region ◽  
Ribosomal Proteins ◽  
Protein Translation ◽  
Messenger Rnas ◽  
Coding Region ◽  
Rna Helicases ◽  
Energy Consuming ◽  
Enzyme Families ◽  
Aaa Atpases

Ribosomal proteins (RPs) are mostly derived from the energy-consuming enzyme families such as ATP-dependent RNA helicases, AAA-ATPases, GTPases and kinases, and are important structural components of the ribosome, which is a supramolecular ribonucleoprotein complex, composed of Ribosomal RNA (rRNA) and RPs, coordinates the translation and synthesis of proteins with the help of transfer RNA (tRNA) and other factors. Not all RPs are indispensable; in other words, the ribosome could be functional and could continue the translation of proteins instead of lacking in some of the RPs. However, the lack of many RPs could result in severe defects in the biogenesis of ribosomes, which could directly influence the overall translation processes and global expression of the proteins leading to the emergence of different diseases including cancer. While microRNAs (miRNAs) are small non-coding RNAs and one of the potent regulators of the post-transcriptional gene expression, miRNAs regulate gene expression by targeting the 3′ untranslated region and/or coding region of the messenger RNAs (mRNAs), and by interacting with the 5′ untranslated region, and eventually finetune the expression of approximately one-third of all mammalian genes. Herein, we highlighted the significance of miRNAs mediated regulation of RPs coding mRNAs in the global protein translation.

scholarly journals The Alternative Noncoding Exons 1 of Aromatase (Cyp19) Gene Modulate Gene Expression in a Posttranscriptional Manner

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3301-3307 ◽  
Author(s):  
Hanzhou Wang ◽  
Rong Li ◽  
Yanfen Hu
Keyword(s):  
Gene Expression ◽  
Posttranscriptional Regulation ◽  
Rna Stability ◽  
Postmenopausal Breast Cancer ◽  
Protein Translation ◽  
Protein Product ◽  
Expression Vectors ◽  
Coding Region ◽  
Tissue Specific ◽  
Exon 1

Aromatase (Cyp19) is a key enzyme in estrogen biosynthesis and an important target in endocrine therapy for estrogen receptor (ER)-positive postmenopausal breast cancer. Aromatase transcription is driven by multiple tissue-specific promoters, which result in the production of various mRNA transcripts that contain an alternative noncoding exon 1 followed by a common protein-coding region. Transcriptional activity of these promoters is the only known determinant for aromatase protein abundance in a given tissue or cellular context. To determine whether aromatase expression could be influenced by additional regulatory mechanisms, we used a common heterologous promoter to drive the expression of multiple aromatase cDNA sequences that differ only by the alternative exon 1 sequence. These expression vectors gave rise to vastly different levels of aromatase mRNA and protein in multiple cell lines examined. Furthermore, the relative abundance of several mRNA variants did not correlate with that of the corresponding protein product. The variation in mRNA and protein levels is most likely due to a negative effect of certain alternative exons 1 on RNA stability and protein translation. Deletional analyses indicate that the 5′ regions of the adipose tissue-specific exons I.3 and I.4 contain the cis-acting elements responsible for modulation of aromatase levels. Thus, our work uncovers an important role of the alternative exons 1 in posttranscriptional regulation of aromatase gene expression.

Effect of intestinal bypass on the expression of actin mRNA in ileal smooth muscle

1990 ◽  
Vol 258 (1) ◽  
pp. R39-R43
Author(s):  
M. Lai ◽  
D. B. Thomason ◽  
N. W. Weisbrodt
Keyword(s):  
Smooth Muscle ◽  
Untranslated Region ◽  
Smooth Muscle Actin ◽  
Intestinal Bypass ◽  
Messenger Rnas ◽  
Muscle Actin ◽  
Coding Region ◽  
Alpha Smooth Muscle Actin ◽  
Actin Isoforms ◽  
Actin Mrna

In this study, messenger RNAs (mRNAs) for actin isoforms were assessed in longitudinal smooth muscle from the ileum of unoperated rats and from rats that had undergone bypass of the middle 70% of the small intestine. The plasmid clone pGEM 10C, which contains a DNA insert complementary to the 3' untranslated region and the region of mRNA that codes for the synthesis of alpha-smooth muscle actin protein, was used to synthesize two riboprobes. One probe, complementary to the coding region of the insert, hybridizes to most, if not all, actin isoform mRNAs. The second probe, complementary to the 3' untranslated region of the insert, hybridizes only to alpha-smooth muscle actin mRNA. RNA was isolated from animals 4 to 5 days after operation, size fractionated by denaturing gel electrophoresis, transferred to nylon membranes, and exposed to the two 32P-labeled riboprobes. Both probes hybridized to RNA of about 1.3 kilobases long. Longitudinal muscle from both groups of animals contained alpha-smooth muscle actin mRNA as well as mRNA for other actin isoforms. Dot blots of varying amounts of RNA were hybridized to the riboprobes to determine the proportions of actin mRNAs. The content and concentration of mRNAs for all actins, and of mRNA for alpha-smooth muscle actin, were significantly greater in muscle from the functioning ileum of bypassed animals 4-5 days after the operation. Thus the operation induces a rapid, specific activation of these contractile protein genes.

Ribosomal flavours: an acquired taste for specific mRNAs?

2018 ◽  
Vol 46 (6) ◽  
pp. 1529-1539 ◽  
Author(s):  
Christian Bates ◽  
Simon J. Hubbard ◽  
Mark P. Ashe
Keyword(s):  
Gene Expression ◽  
Ribosomal Proteins ◽  
Historical Perspective ◽  
Messenger Rnas ◽  
Cell Type ◽  
Ribosomal Rnas ◽  
Functional Consequences ◽  
Specific Mrnas ◽  
Cell Type Specific ◽  
Covalent Modifications

The regulation of translation is critical in almost every aspect of gene expression. Nonetheless, the ribosome is historically viewed as a passive player in this process. However, evidence is accumulating to suggest that variations in the ribosome can have an important influence on which mRNAs are translated. Scope for variation is provided via multiple avenues, including heterogeneity at the level of both ribosomal proteins and ribosomal RNAs and their covalent modifications. Together, these variations provide the potential for hundreds, if not thousands, of flavours of ribosome, each of which could have idiosyncratic preferences for the translation of certain messenger RNAs. Indeed, perturbations to this heterogeneity appear to affect specific subsets of transcripts and manifest as cell-type-specific diseases. This review provides a historical perspective of the ribosomal code hypothesis, before outlining the various sources of heterogeneity, their regulation and functional consequences for the cell.

3′-Untranslated region of the type 2 bradykinin receptor is a potent regulator of gene expression

2006 ◽  
Vol 290 (2) ◽  
pp. F456-F464 ◽  
Author(s):  
Rocio Zamorano ◽  
Sunil Suchindran ◽  
James V. Gainer
Keyword(s):  
Gene Expression ◽  
Untranslated Region ◽  
Tandem Repeats ◽  
Heterologous Gene Expression ◽  
Mrna Level ◽  
Human Kidney ◽  
Variable Number ◽  
Negative Regulator ◽  
Coding Region

Regulation of the constitutively expressed type 2 bradykinin (B2) receptor, which mediates the principal actions of bradykinin, occurs at multiple levels. The goal of the current study was to determine whether the human B2 3′-untranslated region (UTR) has effects on gene expression, with particular focus on the variable number of tandem repeats (B2-VNTR) polymorphic portion of the 3′-UTR and its flanking AU-rich elements (AREs). When inserted downstream of the luciferase coding region of the pGL3-Promoter vector, the B2-VNTR reduced reporter gene activity by 85% compared with pGL3-Promoter alone (promoter control; P < 0.001), an effect that was not appreciably affected by mutation of the flanking AREs. The negative regulatory effects of the B2-VNTR region were position and orientation dependent and strongly positively correlated with the number of tandem repeats in the B2-VNTR region ( r = 0.85, P < 0.001). With respect to mechanism, quantitative RT-PCR revealed that the B2-VNTR mRNA level was 32% of that of promoter control ( P = 0.008), whereas the number of polyadenylated transcripts was 4% ( P = 0.02). In contrast, the mRNA half-life of the B2-VNTR was increased (B2-VNTR: 14.9 vs. promoter control: 12.2 h, P = 0.009). Transient transfection of human kidney-derived tsA201 cells with the B2-VNTR construct increased transcription of the native B2 receptor mRNA by 43% ( P < 0.05), supporting an endogenous B2 receptor-regulatory capacity of the B2-VNTR. In conclusion, these results identify novel pretranslational effects of the B2-VNTR region to act as a potent negative regulator of heterologous gene expression and support the notion that the bradykinin B2 3′-UTR may impact endogenous receptor regulation.

The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

2019 ◽  
Vol 19 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Yuangang Wu ◽  
Xiaoxi Lu ◽  
Bin Shen ◽  
Yi Zeng
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Extracellular Matrix ◽  
Inflammatory Reaction ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Translation ◽  
Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

scholarly journals Organellar Introns in Fungi, Algae, and Plants

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2001
Author(s):  
Jigeesha Mukhopadhyay ◽  
Georg Hausner
Keyword(s):  
Gene Expression ◽  
Ribosomal Proteins ◽  
Heterologous Gene Expression ◽  
Group I Introns ◽  
Group Ii Introns ◽  
Homing Endonucleases ◽  
Organellar Genomes ◽  
Chloroplast Genomes ◽  
Group I ◽  
Group Ii

Introns are ubiquitous in eukaryotic genomes and have long been considered as ‘junk RNA’ but the huge energy expenditure in their transcription, removal, and degradation indicate that they may have functional significance and can offer evolutionary advantages. In fungi, plants and algae introns make a significant contribution to the size of the organellar genomes. Organellar introns are classified as catalytic self-splicing introns that can be categorized as either Group I or Group II introns. There are some biases, with Group I introns being more frequently encountered in fungal mitochondrial genomes, whereas among plants Group II introns dominate within the mitochondrial and chloroplast genomes. Organellar introns can encode a variety of proteins, such as maturases, homing endonucleases, reverse transcriptases, and, in some cases, ribosomal proteins, along with other novel open reading frames. Although organellar introns are viewed to be ribozymes, they do interact with various intron- or nuclear genome-encoded protein factors that assist in the intron RNA to fold into competent splicing structures, or facilitate the turn-over of intron RNAs to prevent reverse splicing. Organellar introns are also known to be involved in non-canonical splicing, such as backsplicing and trans-splicing which can result in novel splicing products or, in some instances, compensate for the fragmentation of genes by recombination events. In organellar genomes, Group I and II introns may exist in nested intronic arrangements, such as introns within introns, referred to as twintrons, where splicing of the external intron may be dependent on splicing of the internal intron. These nested or complex introns, with two or three-component intron modules, are being explored as platforms for alternative splicing and their possible function as molecular switches for modulating gene expression which could be potentially applied towards heterologous gene expression. This review explores recent findings on organellar Group I and II introns, focusing on splicing and mobility mechanisms aided by associated intron/nuclear encoded proteins and their potential roles in organellar gene expression and cross talk between nuclear and organellar genomes. Potential application for these types of elements in biotechnology are also discussed.

scholarly journals The transcription factor SlHY5 regulates the ripening of tomato fruit at both the transcriptional and translational levels

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Weihao Wang ◽  
Peiwen Wang ◽  
Xiaojing Li ◽  
Yuying Wang ◽  
Shiping Tian ◽  
...  
Keyword(s):  
Fruit Ripening ◽  
Nutritional Quality ◽  
Ribosomal Proteins ◽  
Anthocyanin Biosynthesis ◽  
Tomato Fruit ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Protein Translation ◽  
Transcriptional Level ◽  
Translation Efficiency

AbstractLight plays a critical role in plant growth and development, but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown. Here, we found that ELONGATED HYPOCOTYL 5 (HY5), a master regulator in the light signaling pathway, is required for normal fruit ripening in tomato (Solanum lycopersicum). Loss of function of tomato HY5 (SlHY5) impairs pigment accumulation and ethylene biosynthesis. Transcriptome profiling identified 2948 differentially expressed genes, which included 1424 downregulated and 1524 upregulated genes, in the Slhy5 mutants. In addition, genes involved in carotenoid and anthocyanin biosynthesis and ethylene signaling were revealed as direct targets of SlHY5 by chromatin immunoprecipitation. Surprisingly, the expression of a large proportion of genes encoding ribosomal proteins was downregulated in the Slhy5 mutants, and this downregulation pattern was accompanied by a decrease in the abundance of ribosomal proteins. Further analysis demonstrated that SlHY5 affected the translation efficiency of numerous ripening-related genes. These data indicate that SlHY5 regulates fruit ripening both at the transcriptional level by targeting specific molecular pathways and at the translational level by affecting the protein translation machinery. Our findings unravel the regulatory mechanisms of SlHY5 in controlling fruit ripening and nutritional quality and uncover the multifaceted regulation of gene expression by transcription factors.

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