scholarly journals Current View of microRNA Processing

2016 ◽  
Vol 5 ◽  
pp. STI.S12317 ◽  
Author(s):  
Shuai Jiang ◽  
Wei Yan
Keyword(s):  
Rna Polymerase Ii ◽  
Mirna Gene ◽  
Current View ◽  
Regulate Gene Expression ◽  
Mirna Processing ◽  
Functional Roles ◽  
Alternative Processing ◽  
Evolutionarily Conserved ◽  
Processing Pathways ◽  
Microrna Processing

Small evolutionarily conserved noncoding RNAs, microRNAs (miRNAs), regulate gene expression either by translational repression or by mRNA degradation in mammals. miRNAs play functional roles in diverse physiological and pathological processes. miRNA processing is accurately regulated through multifarious factors. The canonical miRNA processing pathway consists of four sequential steps: (a) miRNA gene is transcribed into primary miRNA (pri-miRNA) mainly by RNA polymerase II; (b) pri-miRNA is processed into precursor miRNA (pre-miRNA) through microprocessor complex; (c) pre-miRNA is exported from the nucleus to the cytoplasm with the assistance of Exportin 5 (EXP5/XP05) protein; and (d) pre-miRNA is further processed into mature miRNA via Dicer. Emerging evidence has also demonstrated that some miRNAs undergo alternative processing pathways. Dysregulation of miRNA processing is closely related to tumorigenesis. Here, we review the current advances in the knowledge of miRNA processing and briefly discuss its impact on human cancers.

scholarly journals The NF90-NF45 Complex Functions as a Negative Regulator in the MicroRNA Processing Pathway

2009 ◽  
Vol 29 (13) ◽  
pp. 3754-3769 ◽  
Author(s):  
Shuji Sakamoto ◽  
Kazuma Aoki ◽  
Takuma Higuchi ◽  
Hiroshi Todaka ◽  
Keiko Morisawa ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Binding Activity ◽  
Negative Regulator ◽  
Mirna Biogenesis ◽  
Mirna Processing ◽  
Regulatory Machinery ◽  
Complex Functions ◽  
Microprocessor Complex ◽  
Microrna Processing

ABSTRACT The positive regulatory machinery in the microRNA (miRNA) processing pathway is relatively well characterized, but negative regulation of the pathway is largely unknown. Here we show that a complex of nuclear factor 90 (NF90) and NF45 proteins functions as a negative regulator in miRNA biogenesis. Primary miRNA (pri-miRNA) processing into precursor miRNA (pre-miRNA) was inhibited by overexpression of the NF90 and NF45 proteins, and considerable amounts of pri-miRNAs accumulated in cells coexpressing NF90 and NF45. Treatment of cells overexpressing NF90 and NF45 with an RNA polymerase II inhibitor, α-amanitin, did not reduce the amounts of pri-miRNAs, suggesting that the accumulation of pri-miRNAs is not due to transcriptional activation. In addition, the NF90 and NF45 complex was not found to interact with the Microprocessor complex, which is a processing factor of pri-miRNAs, but was found to bind endogenous pri-miRNAs. NF90-NF45 exhibited higher binding activity for pri-let-7a than pri-miR-21. Of note, depletion of NF90 caused a reduction of pri-let-7a and an increase of mature let-7a miRNA, which has a potent antiproliferative activity, and caused growth suppression of transformed cells. These findings suggest that the association of the NF90-NF45 complex with pri-miRNAs impairs access of the Microprocessor complex to the pri-miRNAs, resulting in a reduction of mature miRNA production.

scholarly journals DRB1 as a mediator between transcription and microRNA processing

2019 ◽  
Author(s):  
Dawid Bielewicz ◽  
Jakub Dolata ◽  
Mateusz Bajczyk ◽  
Lukasz Szewc ◽  
Tomasz Gulanicz ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Mirna Biogenesis ◽  
Transcriptional Level ◽  
Core Component ◽  
Double Stranded Rna ◽  
Mirna Processing ◽  
It Impacts ◽  
Microrna Processing

AbstractDRB1 (HYL1) is a double-stranded RNA binding protein involved in miRNA processing in plants. It is a core component of the Microprocessor complex and enhances the efficiency and precision of miRNA processing by DCL1 protein. In this work, we report a novel function of DRB1 protein in the transcription of MIR genes. DRB1 co-localizes with RNA Polymerase II and affects its distribution along MIR genes. Moreover, proteomic experiments revealed that DRB1 protein interacts with many transcription factors. Finally, we show that the action of DRB1 is not limited to MIR genes as it impacts expression of many other genes, majority of which are involved in plant response to light. These discoveries add DRB1 as another player of gene regulation at transcriptional level, independent of its role in miRNA biogenesis.

scholarly journals Intergenic RNA mainly derives from nascent transcripts of known genes

2020 ◽  
Author(s):  
Agostini Federico ◽  
Zagalak Julian ◽  
Attig Jan ◽  
Ule Jernej ◽  
Nicholas M. Luscombe
Keyword(s):  
Rna Polymerase Ii ◽  
Human Genome ◽  
Genomic Context ◽  
Alternative Processing ◽  
Intergenic Regions ◽  
Transcriptional Units ◽  
And Function ◽  
Cellular Compartments ◽  
Nascent Transcripts ◽  
Transcriptional Start Sites

AbstractBackgroundEukaryotic genomes undergo pervasive transcription, leading to the production of many types of stable and unstable RNAs. Transcription is not restricted to regions with annotated gene features but includes almost any genomic context. Currently, the source and function of most RNAs originating from intergenic regions in the human genome remains unclear.ResultsWe hypothesised that many intergenic RNA can be ascribed to the presence of as-yet unannotated genes or the ‘fuzzy’ transcription of known genes that extends beyond the annotated boundaries. To elucidate the contributions of these two sources, we assembled a dataset of >2.5 billion publicly available RNA-seq reads across 5 human cell lines and multiple cellular compartments to annotate transcriptional units in the human genome. About 80% of transcripts from unannotated intergenic regions can be attributed to the fuzzy transcription of existing genes; the remaining transcripts originate mainly from putative long non-coding RNA loci that are rarely spliced. We validated the transcriptional activity of these intergenic RNA using independent measurements, including transcriptional start sites, chromatin signatures, and genomic occupancies of RNA polymerase II in various phosphorylation states. We also analysed the nuclear localisation and sensitivities of intergenic transcripts to nucleases to illustrate that they tend to be rapidly degraded either ‘on-chromatin’ by XRN2 or ‘off-chromatin’ by the exosome.ConclusionsWe provide a curated atlas of intergenic RNAs that distinguishes between alternative processing of well annotated genes from independent transcriptional units based on the combined analysis of chromatin signatures, nuclear RNA localisation and degradation pathways.

scholarly journals Characterization of the soluble, secreted form of urinary meprin

1996 ◽  
Vol 315 (2) ◽  
pp. 461-465 ◽  
Author(s):  
Robert J. BEYNON ◽  
Simon OLIVER ◽  
Duncan H. L. ROBERTSON
Keyword(s):  
Proteolytic Activity ◽  
Protein Band ◽  
Peptide Sequence ◽  
Soluble Form ◽  
Α Subunit ◽  
Alternative Processing ◽  
Sds Page ◽  
Processing Pathways ◽  
Membrane Bound

A soluble form of the kidney membrane metalloendopeptidase, meprin, is present in urine. Urinary meprin is expressed in BALB/C mice with the Mep-1a/a genotype (high meprin, expressing meprin-α and meprin-β) but not in BALB.K mice of the Mep-1b/b genotype (that only express meprin-β). Western blotting with antisera specific to the meprin-α and the meprin-β subunits established that the only form of meprin present in urine samples was derived from meprin-α. This form of meprin is partially active, and comprises at least three variants by non-reducing SDS/PAGE and by zymography and two protein bands on reducing SDS/PAGE. Sequencing of these two bands established that the N-terminus of the larger protein band begins with the pro-peptide sequence of the α-subunit (VSIKH..), whereas the smaller band possessed the mature meprin N-terminal sequence (NAMRDP..). Trypsin is able to remove the pro-peptide, with a concomitant activation in proteolytic activity. After deglycosylation, the size of the pro- and mature forms of urinary meprin are consistent with cleavage in the region of the X–I boundary. There is a pronounced sexual dimorphism in urinary meprin expression. Females secrete a slightly larger form, and its proteolytic activity is about 50% of that released by males. The urinary meprin is therefore a naturally occurring secreted form of this membrane-bound metalloendopeptidase and is more likely to be generated by alternative processing pathways than by specific release mechanisms.

scholarly journals Characterizing novel olfactory receptors expressed in the murine renal cortex

2019 ◽  
Vol 317 (1) ◽  
pp. F172-F186 ◽  
Author(s):  
Victoria L. Halperin Kuhns ◽  
Jason Sanchez ◽  
Dylan C. Sarver ◽  
Zoya Khalil ◽  
Premraj Rajkumar ◽  
...  
Keyword(s):  
Renal Cortex ◽  
Olfactory Receptors ◽  
Future Research ◽  
Orphan Receptors ◽  
Functional Roles ◽  
Human Orthologs ◽  
Evolutionarily Conserved ◽  
Human Ortholog ◽  
G Protein Coupled

The kidney uses specialized G protein-coupled receptors, including olfactory receptors (ORs), to act as sensors of molecules and metabolites. In the present study, we cloned and studied seven renal ORs, which we previously found to be expressed in the murine renal cortex. As most ORs are orphan receptors, our goal was to identify ligands for these ORs in the hope that this will guide future research into their functional roles. We identified novel ligands for two ORs: Olfr558 and Olfr90. For Olfr558, we confirmed activation by previously reported ligands and identified 16 additional carboxylic acids that activated this OR. The strongest activation of Olfr558 was produced by butyric, cyclobutanecarboxylic, isovaleric, 2-methylvaleric, 3-methylvaleric, 4-methylvaleric, and valeric acids. The primary in vivo source of both butyric and isovaleric acids is gut microbial metabolism. We also identified 14 novel ligands that activated Olfr90, the strongest of which were 2-methyl-4-propyl-1,3-oxathiane, 1-octen-3-ol, 2-octanol, and 3-octanol. Interestingly, 8 of these 14 ligands are of fungal origin. We also investigated the tissue distribution of these receptors and found that they are each found in a subset of “nonsensory” tissues. Finally, we examined the putative human orthologs of Olfr558 and Olfr90 and found that the human ortholog of Olfr558 (OR51E1) has a similar ligand profile, indicating that the role of this OR is likely evolutionarily conserved. In summary, we examined seven novel renal ORs and identified new ligands for Olfr558 and Olfr90, which imply that both of these receptors serve to detect metabolites produced by microorganisms.

scholarly journals Sir2 Silences Gene Transcription by Targeting the Transition between RNA Polymerase II Initiation and Elongation

2008 ◽  
Vol 28 (12) ◽  
pp. 3979-3994 ◽  
Author(s):  
Lu Gao ◽  
David S. Gross
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Transcriptional Silencing ◽  
Pol Ii ◽  
Initiation Factors ◽  
Lysine Deacetylase ◽  
Evolutionarily Conserved ◽  
Mrna Capping ◽  
Capping Enzyme

ABSTRACT It is well accepted that for transcriptional silencing in budding yeast, the evolutionarily conserved lysine deacetylase Sir2, in concert with its partner proteins Sir3 and Sir4, establishes a chromatin structure that prevents RNA polymerase II (Pol II) transcription. However, the mechanism of repression remains controversial. Here, we show that the recruitment of Pol II, as well as that of the general initiation factors TBP and TFIIH, occurs unimpeded to the silent HMR a 1 and HMLα1/HMLα2 mating promoters. This, together with the fact that Pol II is Ser5 phosphorylated, implies that SIR-mediated silencing is permissive to both preinitiation complex (PIC) assembly and transcription initiation. In contrast, the occupancy of factors critical to both mRNA capping and Pol II elongation, including Cet1, Abd1, Spt5, Paf1C, and TFIIS, is virtually abolished. In agreement with this, efficiency of silencing correlates not with a restriction in Pol II promoter occupancy but with a restriction in capping enzyme recruitment. These observations pinpoint the transition between polymerase initiation and elongation as the step targeted by Sir2 and indicate that transcriptional silencing is achieved through the differential accessibility of initiation and capping/elongation factors to chromatin. We compare Sir2-mediated transcriptional silencing to a second repression mechanism, mediated by Tup1. In contrast to Sir2, Tup1 prevents TBP, Pol II, and TFIIH recruitment to the HMLα1 promoter, thereby abrogating PIC formation.

scholarly journals Human histone H3K79 methyltransferase DOT1L protein binds actively transcribing RNA polymerase II to regulate gene expression.

2013 ◽  
Vol 288 (1) ◽  
pp. 295-295
Author(s):  
Seung-Kyoon Kim ◽  
Inkyung Jung ◽  
Hosuk Lee ◽  
Keunsoo Kang ◽  
Mirang Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Regulate Gene Expression ◽  
Regulate Gene

scholarly journals Human Histone H3K79 Methyltransferase DOT1L Methyltransferase Binds Actively Transcribing RNA Polymerase II to Regulate Gene Expression

2012 ◽  
Vol 287 (47) ◽  
pp. 39698-39709 ◽  
Author(s):  
Seung-Kyoon Kim ◽  
Inkyung Jung ◽  
Hosuk Lee ◽  
Keunsoo Kang ◽  
Mirang Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Regulate Gene Expression ◽  
Regulate Gene

GATA factors in vertebrate heart development and disease

2006 ◽  
Vol 8 (22) ◽  
pp. 1-20 ◽  
Author(s):  
Alison Brewer ◽  
John Pizzey
Keyword(s):  
Transcription Factors ◽  
Heart Development ◽  
Regulatory Networks ◽  
Cardiac Development ◽  
Cellular Mechanisms ◽  
Cardiac Morphogenesis ◽  
Functional Roles ◽  
Gata Factors ◽  
Evolutionarily Conserved ◽  
Heart Formation

Vertebrate heart formation is dependent upon complex hierarchical gene regulatory networks, which effect both the specification and differentiation of cardiomyocytes and subsequently cardiac morphogenesis. GATA-4, -5 and -6 comprise an evolutionarily conserved subfamily of transcription factors, which are expressed within the precardiac mesoderm from early stages in its specification and continue to be expressed within the adult heart. We review here the functional roles of individual GATA transcription factors in cardiac development, normal homeostasis and disease. We also review the cellular mechanisms employed to regulate the expression and downstream targets of the different GATA factors.

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