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miRNA biogenesis

Karen E Hayes, Jamie A Barr, Mingyi Xie, Joan A Steitz, Ivan Martinez
Cellular quiescence (also known as G0 arrest) is characterized by reduced DNA replication, increased autophagy, and increased expression of cyclin-dependent kinase p27Kip1 . Quiescence is essential for wound healing, organ regeneration, and preventing neoplasia. Previous findings indicate that microRNAs (miRNAs) play an important role in regulating cellular quiescence. Our recent publication demonstrated the existence of an alternative miRNA biogenesis pathway in primary human foreskin fibroblast (HFF) cells during quiescence...
February 5, 2018: Bio-protocol
Zhenfei Sun, Min Li, Ying Zhou, Tongtong Guo, Yin Liu, Hui Zhang, Yuda Fang
Light and microRNAs (miRNAs) are key external and internal signals for plant development, respectively. However, the relationship between the light signaling and miRNA biogenesis pathways remains unknown. Here we found that miRNA processer proteins DCL1 and HYL1 interact with a basic helix-loop-helix (bHLH) transcription factor, phytochrome-interacting factor 4 (PIF4), which mediates the destabilization of DCL1 during dark-to-red-light transition. PIF4 acts as a transcription factor for some miRNA genes and is necessary for the proper accumulation of miRNAs...
March 9, 2018: PLoS Genetics
Eek-Hoon Jho
Since the first component of Hippo signaling, Wts in Drosophila, was identified in 1995, the progress of Hippo signaling studies has been very slow initially. However, after the findings suggesting that the core kinase pathway established in Drosophila was evolutionarily conserved in metazoans for the determination of organ size around 2008, the number of publications related to Hippo signaling has grown exponentially. Identification of molecular mechanisms underlying Hippo signaling response to intrinsic cues, such as cell-cell contact and mechanotransduction, as well as extrinsic cues, such as nutrients and soluble factors, has been one of the key topics of Hippo signaling...
March 9, 2018: BMB Reports
Pushpendra Pratap, Syed Tasleem Raza, Shania Abbas, Farzana Mahdi
Lung carcinoma is the leading cause of cancer-related death worldwide; it has been regarded as the origin of death by melanoma universally. Frequently, lung carcinomas identified in progressive phase and have lowermost roots of existence in any category of the cancer. MicroRNAs (miRNAs) are small having 18-25 nucleotides extended noncoding RNAs regulating gene expression and elaborate in a wide assortment of cellular progressions also. Cumulative indications propose that, miRNA plays imperative and multifarious roles in cases of human lung cancer genetics...
January 2018: Journal of Cancer Research and Therapeutics
Dan Liu, Li Zhu, Tong Ni, Fang-Lin Guan, Yan-Jiong Chen, Dong-Liang Ma, Eyleen L K Goh, Teng Chen
microRNA (miRNA) play important roles in drug addiction and act as a post-transcriptional regulator of gene expression. We previously reported extensive downregulation of miRNAs in the nucleus accumbens (NAc) of methamphetamine (METH)-sensitized mice. However, the regulatory mechanism of this METH-induced downregulation of miRNAs has yet to be elucidated. Thus, we examined METH-induced changes in the expression of miRNAs and their precursors, as well as the expression levels of mRNA and the proteins involved in miRNA biogenesis such as Dicer1 and Ago2, in the nucleus accumbens of METH-induced locomotor sensitized mice...
March 8, 2018: Addiction Biology
Shubaash Anthiya, Audrey Griveau, Claire Loussouarn, Patrick Baril, Martin Garnett, Jean-Paul Issartel, Emmanuel Garcion
MicroRNAs (miRNAs) are key regulatory elements encoded by the genome. A single miRNA can downregulate the expression of multiple genes involved in diverse functions. Because cancer is a disease with multiple gene aberrations, developing novel approaches to identify and modulate miRNA pathways may result in a breakthrough for cancer treatment. With a special focus on glioblastoma (GBM), this review provides an up-to-date summary of miRNA biogenesis, the role of miRNA in cancer resistance, and essential tools for modulating miRNA expression, as well as of clinically promising RNAi delivery systems and how they can be adapted for therapy...
March 2018: Trends in Cancer
Igor I Titov, Pavel S Vorozheykin
BACKGROUND: MicroRNAs proceeds through the different canonical and non-canonical pathways; the most frequent of the non-canonical ones is the splicing-dependent biogenesis of mirtrons. We compare the mirtrons and non-mirtrons of human and mouse to explore how their maturation appears in the precursor structure around the miRNA. RESULTS: We found the coherence of the overhang lengths what indicates the dependence between the cleavage sites. To explain this dependence we suggest the 2-lever model of the Dicer structure that couples the imprecisions in Drosha and Dicer...
February 9, 2018: BMC Genomics
P M Clark, N Chitnis, M Shieh, M Kamoun, F B Johnson, D Monos
The MHC is recognized for its importance in human health and disease. However, many disease-associated variants throughout the region remain of unknown significance, residing predominantly within non-coding regions of the MHC. The characterization of non-coding RNA transcripts throughout the MHC is thus central to understanding the genetic contribution of these variants. Therefore, we characterize novel miRNA transcripts throughout the MHC by performing deep RNA sequencing of two B lymphoblastoid cell lines with completely characterized MHC haplotypes...
March 1, 2018: Scientific Reports
Alexandra Iulia Irimie, Alina-Andreea Zimta, Cristina Ciocan, Nikolay Mehterov, Diana Dudea, Cornelia Braicu, Ioana Berindan-Neagoe
Previously ignored non-coding RNAs (ncRNAs) have become the subject of many studies. However, there is an imbalance in the amount of consideration that ncRNAs are receiving. Some transcripts such as microRNAs (miRNAs) or small interfering RNAs (siRNAs) have gained much attention, but it is necessary to investigate other "pieces of the RNA puzzle". These can offer a more complete view over normal and pathological cell behavior. The other ncRNA species are less studied, either due to their recent discovery, such as stable intronic sequence RNA (sisRNA), YRNA, miRNA-offset RNAs (moRNA), telomerase RNA component (TERC), natural antisense transcript (NAT), transcribed ultraconserved regions (T-UCR), and pseudogene transcript, or because they are still largely seen as non-coding transcripts with no relevance to pathogenesis...
March 1, 2018: Genes
Yao Song, Wei Feng, Guo-Min Shi, Chao Chen, You-Yi Zhang
MicroRNAs (miRNAs) are small noncoding RNAs that control diverse cellular and developmental events through repression of large sets of target mRNAs. miRNAs expressions were mainly regulated at two levels: transcriptional and post-transcriptional. Transcriptional regulation of miRNA-encoding genes produce specific expression patterns of individual miRNA. However, the mechanism of post-transcriptional regulation of miRNAs remains largely unknown. The present study was aimed to clarify whether HuR, an evolutionary conserved AU-rich binding protein, could regulate miRNAs expressions...
February 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Qi Tang, Lipeng Qiu, Guohui Li
MicroRNAs (miRNAs) are a class of non-coding RNAs with ∼22 nucleotides, which are able to regulate various biological processes, including the viral life cycle and host-pathogen interactions. Long primary transcripts (pri-miRNAs) are initially transcribed in nucleus, and subsequently processed by Dicer in cytoplasm to generate mature miRNAs. Baculoviruses consist of large, enveloped, insect-pathogenic viruses with a double-stranded circular DNA genome. Recent studies suggest that baculoviruses encode some miRNAs to manipulate expression regulation of host genes, whereas host modulate viral gene expression via miRNAs to limit viral infection...
February 27, 2018: Current Microbiology
Sri Ramulu N Pullagura, Bill Buaas, Nichelle Gray, Lindsey C Krening, Anuj Srivastava, Robert E Braun
Several in vitro studies suggest canonical miRNA biogenesis requires the DICER co-factors TARBP2 and PRKRA for processing of pre-miRNAs to mature miRNAs. To investigate the roles of TARBP2 and PRKRA in miRNA biogenesis in vivo , and to determine possible functional redundancy, we first compared the phenotypes of Tarbp2 and Prkra single and double-mutants. In contrast to Dicer-/- embryos, which die by E7.5, single Tarbp2-/- and Prkra-/- mice survive beyond E7.5 and either die peri-natally, or survive and exhibit cranial/facial abnormalities, respectively...
February 21, 2018: Genetics
T A Shtam, R A Samsonov, A V Volnitskiy, R A Kamyshinsky, N A Verlov, M S Kniazeva, E A Korobkina, A S Orehov, A L Vasiliev, A L Konevega, A V Malek
Extracellular vesicles (EV) are secreted by cells of multicellular organisms. EV mediate specific mode of intercellular communication by "horizontal" exchange of substances and information. This phenomenon seems to have an essential biological significance and became a subject of intensive research. Biogenesis, structural and functional features of the EV is being commonly studies in in vitro condition. Several methods of EV isolation from cell culture medium are established, however selection of method might influence on obtained results...
January 2018: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
Jessica Mingardi, Laura Musazzi, Giuseppina De Petro, Alessandro Barbon
Post-transcriptional modifications are essential mechanisms for mRNA biogenesis and function in eukaryotic cells. Beyond well-characterized events such as splicing, capping, and polyadenylation, there are several others, as RNA editing mechanisms and regulation of transcription mediated by miRNAs that are taking increasing attention in the last years. RNA editing through A-to-I deamination increases transcriptomic complexity, generating different proteins with amino acid substitution from the same transcript...
February 19, 2018: Molecular Neurobiology
José Manuel Matamala, Raul Arias-Carrasco, Carolina Sanchez, Markus Uhrig, Leslie Bargsted, Soledad Matus, Vinicius Maracaja-Coutinho, Sebastian Abarzua, Brigitte van Zundert, Renato Verdugo, Patricio Manque, Claudio Hetz
The occurrence of mutations of TDP-43, FUS, and C9ORF72 in amyotrophic lateral sclerosis (ALS) suggests pathogenic alterations to RNA metabolism and specifically to microRNA (miRNA) biology. Moreover, several ALS-related proteins impact stress granule dynamics affecting miRNA biogenesis and cellular miRNA levels. miRNAs are present in different biological fluids and have been proposed as potential biomarkers. Here we used next-generation sequencing to perform a comparative analysis of the expression profile of circulating miRNAs in the serum of 2 mutant superoxide dismutase 1 transgenic mice...
April 2018: Neurobiology of Aging
Patrick von Born, Marti Bernardo-Faura, Ignacio Rubio-Somoza
Development and fitness of any organism rely on properly controlled gene expression. This is especially true for plants, as their development is determined by both internal and external cues. MicroRNAs (miRNAs) are embedded in the genetic cascades that integrate and translate those cues into developmental programs. miRNAs negatively regulate their target genes mainly post-transcriptionally through two co-existing mechanisms; mRNA cleavage and translational inhibition. Despite our increasing knowledge about the genetic and biochemical processes involved in those concurrent mechanisms, little is known about their relative contributions to the overall miRNA-mediated regulation...
2018: PloS One
Patricia Baldrich, Aleksandra Beric, Blake C Meyers
MicroRNAs (miRNAs) are key regulators of gene expression. A handful of miRNAs are broadly conserved in land plants, while the majority are lineage specific; this review describes the processes by which new miRNAs are hypothesized to have emerged. Two major models describe miRNA origins, firstly, de novo emergence via inverted duplication of target gene fragments, and secondly, the expansion and neofunctionalization of existing miRNA families. The occasional acquisition of target sites by previously un-targeted genes adds further dynamism to the process by which miRNAs may shift roles during evolution...
February 12, 2018: Current Opinion in Plant Biology
Jiao Li, Wenchen Pu, Hui-Lung Sun, Jian-Kang Zhou, Xin Fan, Yuanyuan Zheng, Juan He, Xuesha Liu, Zhichu Xia, Lunxu Liu, Yu-Quan Wei, Yong Peng
MicroRNA (miRNA) dysregulation is associated with the tumorigenesis and development of numerous human cancers. The defect in miRNA biogenesis is the main cause of miRNA dysregulation. We previously demonstrated that ERK-induced phosphorylation of XPO5 followed by peptidyl-prolyl cis/trans isomerase Pin1-mediated isomerization downregulates miRNA expression and contributes to hepatocellular carcinoma (HCC) development. However, how Pin1 precisely regulates miRNA biogenesis in HCC remains elusive. Here we reveal that Pin1 has a pivotal role in the miRNA maturation process by modulating phosphorylated Serine-Proline (pS-P) motif of XPO5 in a phosphorylation-dependent manner...
February 14, 2018: Cell Death and Differentiation
Mariya M Kucherenko, Halyna R Shcherbata
Stress can be temporary or chronic, and mild or acute. Depending on its extent and severity, cells either alter their metabolism, and adopt a new state, or die. Fluctuations in environmental conditions occur frequently, and such stress disturbs cellular homeostasis, but in general, stresses are reversible and last only a short time. There is increasing evidence that regulation of gene expression in response to temporal stress happens post-transcriptionally in specialized subcellular membrane-less compartments called ribonucleoprotein (RNP) granules...
February 14, 2018: Journal of Cell Science
Shengjun Li, Kan Liu, Bangjun Zhou, Mu Li, Shuxin Zhang, Lirong Zeng, Chi Zhang, Bin Yu
MAC3A and MAC3B are conserved U-box containing proteins in eukaryotes. They are subunits of the MOS4-associated complex (MAC) that plays essential roles in plant immunity and development in Arabidopsis. However, their functional mechanisms remain elusive. Here we show that Arabidopsis thaliana MAC3A and MAC3B act redundantly in microRNA (miRNA) biogenesis. Lack of both MAC3A and MAC3B in the mac3b mac3b double mutant reduces the accumulation of miRNAs, causing elevated transcript levels of miRNA targets. mac3a mac3b also decreases the levels of primary miRNA transcripts (pri-miRNAs)...
February 5, 2018: Plant Cell
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