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microRNA biogenesis

Julia K Nussbacher, Gene W Yeo
RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced UV crosslinking followed by immunoprecipitation (eCLIP) datasets for 126 RBPs to discover miR-encoding genomic loci that are statistically enriched for RBP binding. We find that 92% of RBPs interact directly with at least one miR locus, and that some interactions are cell line specific despite expression of the miR locus in both cell lines evaluated...
March 15, 2018: Molecular Cell
Xiao Fu, Mengjie Liu, Shengyang Qu, Jiequn Ma, Yamin Zhang, Tingting Shi, Hongqing Wen, Yujuan Yang, Shuhong Wang, Jing Wang, Kejun Nan, Yu Yao, Tao Tian
BACKGROUND: Multidrug resistance is the main obstacle for hepatocellular carcinoma (HCC) treatment. miR-32-5p is involved in HCC progression but its function in multidrug resistance is still unclear. Here we aim to find out the function of miR-32-5p in inducing multidrug resistance and its underlying mechanisms of transforming sensitive cell to resistant cell. METHODS: We detected the expression of miR-32-5p and PTEN in the multidrug-resistant cell line (Bel/5-FU) and the sensitive cell line (Bel7402), HCC and para-carcinoma liver tissues through real-time PCR...
March 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
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
Frank Curmi, Ruben J Cauchi
Gemin3, also known as DDX20 or DP103, is a DEAD-box RNA helicase which is involved in more than one cellular process. Though RNA unwinding has been determined in vitro , it is surprisingly not required for all of its activities in cellular metabolism. Gemin3 is an essential gene, present in Amoeba and Metazoa. The highly conserved N-terminus hosts the helicase core, formed of the helicase- and DEAD-domains, which, based on crystal structure determination, have key roles in RNA binding. The C-terminus of Gemin3 is highly divergent between species and serves as the interaction site for several accessory factors that could recruit Gemin3 to its target substrates and/or modulate its function...
March 9, 2018: Biochemical Society Transactions
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
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
Barbara Ogórek, Hilaire C Lam, Damir Khabibullin, Heng-Jia Liu, Julie Nijmeh, Robinson Triboulet, David J Kwiatkowski, Richard I Gregory, Elizabeth P Henske
Tuberous Sclerosis Complex (TSC) is an autosomal dominant disease caused by germline inactivating mutations of TSC1 or TSC2. In TSC-associated tumors of the brain, heart, skin, kidney, and lung, inactivation of both alleles of TSC1 or TSC2 leads to hyperactivation of the mTORC1 pathway. The TSC/mTORC1 pathway is a key regulator of cellular processes related to growth, proliferation and autophagy. We and others have previously found that mTORC1 regulates microRNA biogenesis, but the mechanisms are not fully understood...
March 2, 2018: Human Molecular Genetics
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
Gregory R Rompala, Anais Mounier, Cody M Wolfe, Qishan Lin, Iliya Lefterov, Gregg E Homanics
While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm...
2018: Frontiers in Genetics
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
Lucile Fressigné, Martin J Simard
In recent years, the discovery of small non-coding RNAs has opened an all new field in molecular biology. Indeed, these non-coding sequences give rise to powerful regulators of gene expression. Nowadays, different types of small non-coding RNAs have been described. Of these, the best-characterized types are microRNAs, piRNAs (Piwi-interacting RNAs) and siRNAs (small interfering RNAs). Because of their fine-tuning important function in the regulation of gene and genome expression, an aberrant expression level of those small non-coding RNAs are associated to several pathologies...
February 2018: Médecine Sciences: M/S
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
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