scholarly journals microRNA seedless sites attenuate strong-seed-site-mediated target repression

2019 ◽  
Author(s):  
Xujun Wang ◽  
Jingru Tian ◽  
Peng Cui ◽  
Stephen Mastriano ◽  
Dingyao Zhang ◽  
...  
Keyword(s):  
Protein Translation ◽  
Untranslated Regions ◽  
Seed Region ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Attenuation Effect ◽  
Reporter Assays ◽  
Regulate Protein ◽  
Surprising Finding

AbstractMicroRNAs (miRNAs) regulate protein-coding gene expression primarily through cognitive binding sites in the 3’ untranslated regions (3′ UTRs). Seed sites are sequences in messenger RNAs (mRNAs) that form perfect Watson-Crick base-paring with a miRNA’s seed region, which can effectively reduce mRNA abundance and/or repress protein translation. Some seedless sites, which do no form perfect seed-pairing with a miRNA, can also lead to target repression, often with lower efficacy. Here we report the surprising finding that when seedless sites and seed sites are co-present in the same 3’UTR, seedless sites attenuate strong-seed-site-mediated target suppression, independent of 3′ UTR length. This attenuation effect is detectable in >70% of transcriptomic datasets examined, in which specific miRNAs are experimentally increased or decreased. The attenuation effect is confirmed by 3’UTR reporter assays and mediated through base-pairing between miRNA and seedless sites. Furthermore, this seedless-site-based attenuation effect could affect seed sites of the same miRNA or another miRNA, thus partially explaining the variability in target suppression and miRNA-mediated gene upregulation. Our findings reveal an unexpected principle of miRNA-mediated gene regulation, and could impact the understanding of many miRNA-regulated biological processes.

scholarly journals The Reading Frame Surveillance Hypothesis

2016 ◽  
Author(s):  
John T. Gray
Keyword(s):  
Large Subunit ◽  
Protein Translation ◽  
Small Subunit ◽  
Phenotypic Traits ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Reading Frame ◽  
Mammalian Sperm ◽  
Translation Mechanism

AbbreviationsRFSReading Frame SurveillanceRdRPRNA-dependent RNA PolymerasefrRNAsFraming RNAsLSULarge SubunitSSUSmall SubunittRFTransfer RNA derived FragmentntnucleotideAbstractAn alternative model for protein translation is presented wherein ribosomes utilize a complementary RNA copy of protein coding sequences to monitor the progress of messenger RNAs during their translation to reduce the frequency of frameshifting errors. The synthesis of this ‘framing RNA’ is postulated to be catalyzed by the small subunit of the ribosome, in the decoding center, by excising and concatemerizing tRNA anticodons bound to each codon of the mRNA template. Various components of the model are supported by previous observations of tRNA mutants that impact ribosomal frameshifting, unique globin-coding RNAs in developing erythroblasts, and the epigenetic, intergenerational transfer of phenotypic traits via mammalian sperm RNA. Confirmation of the proposed translation mechanism is experimentally tractable and might significantly enhance our understanding of several fundamental biological processes.

scholarly journals Cell Cycle Control by Nuclear Sequestration ofCDC20andCDH1mRNA in Plant Stem Cells

2017 ◽  
Author(s):  
Weibing Yang ◽  
Raymond Wightman ◽  
Elliot M. Meyerowitz
Keyword(s):  
Cell Cycle ◽  
Nuclear Localization ◽  
Cell Cycle Control ◽  
Protein Translation ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Rna Molecules ◽  
Nuclear Envelope Breakdown ◽  
And Function ◽  
Necessary And Sufficient

AbstractIn eukaryotic cells, most RNA molecules are exported into the cytoplasm after being transcribed in the nucleus. Long noncoding RNAs (lncRNAs) have been found to reside and function primarily inside the nucleus, but nuclear localization of protein-coding messenger RNAs (mRNAs) has been considered rare in both animals and plants. Here we show that two mRNAs, transcribed from theCDC20andCCS52B(plant orthologue ofCDH1) genes, are specifically sequestered inside the nucleus during the cell cycle. CDC20 and CDH1 both function as coactivators of the anaphase-promoting complex or cyclosome (APC/C) E3 ligase to trigger cyclin B (C YCB) destruction. In theArabidopsis thalianashoot apical meristem (SAM), we findCDC20andCCS52Bare co-expressed withCYCBsin mitotic cells.CYCBtranscripts can be exported and translated, whereasCDC20andCCS52BmRNAs are strictly confined to the nucleus at prophase and the cognate proteins are not translated until the redistribution of the mRNAs to the cytoplasm after nuclear envelope breakdown (NEBD) at prometaphase. The 5’ untranslated region (UTR) is necessary and sufficient forCDC20mRNA nuclear localization as well as protein translation. Mitotic enrichment ofCDC20andCCS52Btranscripts enables the timely and rapid activation of APC/C, while their nuclear sequestration at prophase appears to protect cyclins from precocious degradation.

scholarly journals Noncanonical Roles of tRNAs: tRNA Fragments and Beyond

2020 ◽  
Vol 54 (1) ◽  
pp. 47-69 ◽  
Author(s):  
Zhangli Su ◽  
Briana Wilson ◽  
Pankaj Kumar ◽  
Anindya Dutta
Keyword(s):  
Sequence Variation ◽  
Protein Translation ◽  
Nutrient Sensing ◽  
Trna Genes ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Regulatory Pathways ◽  
Transfer Rnas ◽  
Rna Molecules

As one of the most abundant and conserved RNA species, transfer RNAs (tRNAs) are well known for their role in reading the codons on messenger RNAs and translating them into proteins. In this review, we discuss the noncanonical functions of tRNAs. These include tRNAs as precursors to novel small RNA molecules derived from tRNAs, also called tRNA-derived fragments, that are abundant across species and have diverse functions in different biological processes, including regulating protein translation, Argonaute-dependent gene silencing, and more. Furthermore, the role of tRNAs in biosynthesis and other regulatory pathways, including nutrient sensing, splicing, transcription, retroelement regulation, immune response, and apoptosis, is reviewed. Genome organization and sequence variation of tRNA genes are also discussed in light of their noncanonical functions. Lastly, we discuss the recent applications of tRNAs in genome editing and microbiome sequencing.

scholarly journals Competing Endogenous RNA: The Key to Posttranscriptional Regulation

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Rituparno Sen ◽  
Suman Ghosal ◽  
Shaoli Das ◽  
Subrata Balti ◽  
Jayprokas Chakrabarti
Keyword(s):  
Posttranscriptional Regulation ◽  
Circular Rnas ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Protein Coding ◽  
Regulatory Circuit ◽  
Transcriptional Regulatory ◽  
Mirna Sponges ◽  
The Impact

Competing endogenous RNA, ceRNA, vie with messenger RNAs (mRNAs) for microRNAs (miRNAs) with shared miRNAs responses elements (MREs) and act as modulator of miRNA by influencing the available level of miRNA. It has recently been discovered that, apart from protein-coding ceRNAs, pseudogenes, long noncoding RNAs (lncRNAs), and circular RNAs act as miRNA “sponges” by sharing common MRE, inhibiting normal miRNA targeting activity on mRNA. These MRE sharing elements form the posttranscriptional ceRNA network to regulate mRNA expression. ceRNAs are widely implicated in many biological processes. Recent studies have identified ceRNAs associated with a number of diseases including cancer. This brief review focuses on the molecular mechanism of ceRNA as part of the complex post-transcriptional regulatory circuit in cell and the impact of ceRNAs in development and disease.

LncRNA LINC00858 enhances cervical cancer cell growth through miR-3064-5p/ VMA21 axis

2021 ◽  
pp. 1-11
Author(s):  
Min Wei ◽  
Youguo Chen ◽  
Wensheng Du
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Luciferase Reporter ◽  
Cancer Cell Growth ◽  
Protein Coding ◽  
Gynecological Malignancy ◽  
Promising Therapeutic Target ◽  
Proliferation And Apoptosis ◽  
Reporter Assays

BACKGROUND: Cervical cancer (CC) is the most common form of gynecological malignancy. Long intergenic non-protein coding RNA 858 (LINC00858) has been identified to participate in multiple cancers. However, the role and mechanism of LINC00858 in CC cells are still elusive. AIM: The aim of this study is to explore the biological functions and mechanisms of LINC00858 in CC cells. METHODS: RT-qPCR analysis was used to examine the expression of LINC00858 in CC cells. EdU and colony formation assay were utilized to assess cell proliferation. TUNEL assay and flow cytometry assay were conducted to assess cell apoptosis. The mechanism regarding LINC00858 was certified through RNA pull down, RIP and luciferase reporter assays. RESULTS: The up-regulated LINC00858 was detected in CC cells. Reduction of LINC00858 effectively subdued CC cells proliferation and stimulated cell apoptosis. LINC00858 was determined to bind with miR-3064-5p and up-regulate VMA21 in CC cells. In rescue assays, miR-3064-5p down-regulation and VMA21 up-regulation were able to counteract the effect caused by LINC00858 decrease on CC cell proliferation and apoptosis. CONCLUSION: LINC00858 enhances cell proliferation, while restraining cell apoptosis in CC through targeting miR-3064-5p/VMA21 axis, implying that LINC00858 may serve as a promising therapeutic target for CC.

scholarly journals Lamin A/C Is Dispensable to Mechanical Repression of Adipogenesis

2021 ◽  
Vol 22 (12) ◽  
pp. 6580
Author(s):  
Matthew Goelzer ◽  
Amel Dudakovic ◽  
Melis Olcum ◽  
Buer Sen ◽  
Engin Ozcivici ◽  
...  
Keyword(s):  
Cell Structure ◽  
Nuclear Architecture ◽  
Focal Adhesions ◽  
Protein Translation ◽  
Lamin A ◽  
Transcriptional Level ◽  
Rna Seq ◽  
Interferon Signaling ◽  
Regulate Protein ◽  
Low Intensity Vibration

Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C.

scholarly journals Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xiaoli Liu ◽  
Zuwei Yin ◽  
Linping Xu ◽  
Huaimin Liu ◽  
Lifeng Jiang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Bioinformatics Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Hedgehog Pathway ◽  
Biological Processes ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Rip Assay

AbstractLong noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.

Structure and expression of canary myc family genes

1991 ◽  
Vol 11 (3) ◽  
pp. 1770-1776
Author(s):  
R G Collum ◽  
D F Clayton ◽  
F W Alt
Keyword(s):  
Untranslated Region ◽  
Untranslated Regions ◽  
Coding Region ◽  
Protein Coding ◽  
Coding Regions ◽  
Neuronal Precursors ◽  
Myc Gene ◽  
Mature Neurons

We found that the canary N-myc gene is highly related to mammalian N-myc genes in both the protein-coding region and the long 3' untranslated region. Examined coding regions of the canary c-myc gene were also highly related to their mammalian counterparts, but in contrast to N-myc, the canary and mammalian c-myc genes were quite divergent in their 3' untranslated regions. We readily detected N-myc and c-myc expression in the adult canary brain and found N-myc expression both at sites of proliferating neuronal precursors and in mature neurons.

scholarly journals The Roles of MicroRNA-141 in Human Cancers: From Diagnosis to Treatment

2016 ◽  
Vol 38 (2) ◽  
pp. 427-448 ◽  
Author(s):  
Yanping Gao ◽  
Bing Feng ◽  
Siqi Han ◽  
Kai Zhang ◽  
Jing Chen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Untranslated Regions ◽  
Messenger Rnas ◽  
Gene Expressions ◽  
Mesenchymal Transition ◽  
Cellular Processes ◽  
Health Impairment ◽  
Non Coding Rnas ◽  
Human Malignant Tumors

Cancer remains one of the most threatening causes of human health impairment, and the mechanisms underlying tumorigenesis have not been completely characterized. MicroRNAs (miRNAs) are a group of endogenous, small (18∼25 nucleotides) non-coding RNAs which negatively regulate gene expressions by directly binding to the 3'-untranslated regions (3'-UTRs) of the target messenger RNAs (mRNAs). Increasing evidence has demonstrated abnormal miRNA profiles and confirmed their involvement in tumor initiation and progression. As one important member of the miR-200 family, microRNA (miR)-141 is aberrantly expressed in many human malignant tumors, participating in various cellular processes including epithelial-mesenchymal transition (EMT), proliferation, migration, invasion, and drug resistance. In the present review, we briefly describe the mechanisms underlying miR-141-mediated tumorigenesis and the possible future of miR-141 as a potential diagnostic and prognostic parameter as well as therapeutic target in clinical applications.

scholarly journals Promising Advances in LINC01116 Related to Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yating Xu ◽  
Xiao Yu ◽  
Menggang Zhang ◽  
Qingyuan Zheng ◽  
Zongzong Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Lung Cancer ◽  
Cancer Colorectal ◽  
Malignant Tumors ◽  
Biological Processes ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Future Studies ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are RNAs with a length of no less than 200 nucleotides that are not translated into proteins. Accumulating evidence indicates that lncRNAs are pivotal regulators of biological processes in several diseases, particularly in several malignant tumors. Long intergenic non-protein coding RNA 1116 (LINC01116) is a lncRNA, whose aberrant expression is correlated with a variety of cancers, including lung cancer, gastric cancer, colorectal cancer, glioma, and osteosarcoma. LINC01116 plays a crucial role in facilitating cell proliferation, invasion, migration, and apoptosis. In addition, numerous studies have recently suggested that LINC01116 has emerged as a novel biomarker for prognosis and therapy in malignant tumors. Consequently, we summarize the clinical significance of LINC01116 associated with biological processes in various tumors and provide a hopeful orientation to guide clinical treatment of various cancers in future studies.

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