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microRNA biogenesis pathway

Marta Orlicka-Płocka, Dorota Gurda, Agnieszka Fedoruk-Wyszomirska, Iwona Smolarek, Eliza Wyszko
Cardiovascular Diseases (CD) are currently one of the most common causes of death. Because heart related deaths occur on such an enormous scale this phenomenon is referred to as an epidemic. Chronic and acute injury of the heart could be an effect of cardiac remodeling, which is a result of molecular, cellular and interstitial changes, influenced by hemodynamic load or neurohormonal activation (Cohn et al., 2000). These small deviations in cardiac activity and morphology may lead to an enormous negative effect...
October 19, 2016: Acta Biochimica Polonica
Caterina Catalanotto, Carlo Cogoni, Giuseppe Zardo
The finding that small non-coding RNAs (ncRNAs) are able to control gene expression in a sequence specific manner has had a massive impact on biology. Recent improvements in high throughput sequencing and computational prediction methods have allowed the discovery and classification of several types of ncRNAs. Based on their precursor structures, biogenesis pathways and modes of action, ncRNAs are classified as small interfering RNAs (siRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), endogenous small interfering RNAs (endo-siRNAs or esiRNAs), promoter associate RNAs (pRNAs), small nucleolar RNAs (snoRNAs) and sno-derived RNAs...
October 13, 2016: International Journal of Molecular Sciences
Helen L Lightfoot, Eric A Miska, Shankar Balasubramanian
The protein Lin28 and microRNA let-7 play critical roles in mammalian development and human disease. Lin28 inhibits let-7 biogenesis through direct interaction with let-7 precursors (pre-let-7). Accumulating evidence in vitro and in vivo suggests this interaction plays a dominant role in embryonic stem cell self-renewal and tumorigenesis. Thus the Lin28-let-7 interaction might be an attractive drug target, if not for the well-known difficulties in targeting protein-RNA interactions with drugs. The identification and development of suitable probe molecules to further elucidate therapeutic potential, as well as mechanistic details of this pathway will be valuable...
October 12, 2016: Organic & Biomolecular Chemistry
Perrine Rasschaert, Thomas Figueroa, Ginette Dambrine, Denis Rasschaert, Sylvie Laurent
Interplay between alternative splicing and the Microprocessor may have differential effects on the expression of intronic miRNAs organised into clusters. We used a viral model - the LAT long non-coding RNA (LAT lncRNA) of Marek's disease oncogenic herpesvirus (MDV-1), which has the mdv1-miR-M8-M6-M7-M10 cluster embedded in its first intron - to assess the impact of splicing modifications on the biogenesis of each of the miRNAs from the cluster. Drosha silencing and alternative splicing of an extended exon 2 of the LAT lncRNA from a newly identified 3' splice site (SS) at the end of the second miRNA of the cluster showed that mdv1-miR-M6 was a 5'-tailed mirtron...
October 7, 2016: RNA Biology
Erin C Peckham-Gregory, Dharma R Thapa, Jeremy Martinson, Priya Duggal, Sudhir Penugonda, Jay H Bream, Po-Yin Chang, Sugandha Dandekar, Shen-Chih Chang, Roger Detels, Otoniel Martínez-Maza, Zuo-Feng Zhang, Shehnaz K Hussain
BACKGROUND: MicroRNAs, small non-coding RNAs involved in gene regulation, are implicated in lymphomagenesis. We evaluated whether genetic variations in microRNA coding regions, binding sites, or biogenesis genes (collectively referred to as miRNA-SNPs) were associated with risk of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), and serum levels of four lymphoma-related microRNAs. METHODS: Twenty-five miRNA-SNPs were genotyped in 180 AIDS-NHL cases and 529 HIV-infected matched controls from the Multicenter AIDS Cohort Study (MACS), and real-time polymerase chain reaction was used to quantify serum microRNA levels...
October 1, 2016: Cancer Epidemiology
Maryam Majidinia, Bahman Yousefi
The inability of cancer cells in taking care of DNA damages can lead to cancer development and/or progression. Due to the essential role of DNA repair in maintaining genomic stability, tightly controlled regulatory mechanism are required for these processes. Recent studies have shown a myriad of interactions among DNA damage response (DDR) components and miRNAs. While DDR modulates miRNA expression in transcriptional and post-transcriptional levels and affects miRNA degradation, miRNAs in turn, directly modulate the expression of multiple proteins in the DDR pathways, or indirectly fine-tune the expression of such proteins...
September 27, 2016: DNA Repair
Olivia Jerczynski, Nicolas Lacroix-Pépin, Eric Boilard, Ezequiel Calvo, Agathe Bernet, Michel A Fortier, Ida Björkgren, Petra Sipilä, Clémence Belleannée
Dicer1 is an endoribonuclease involved in the biogenesis of functional molecules such as microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs). These small non-coding RNAs are important regulators of post-transcriptional gene expression and participate in the control of male fertility. With the knowledge that 1) Dicer1-dependent factors are required for proper sperm maturation in the epididymis, and that 2) miRNAs are potent mediators of intercellular communication in most biological systems, we investigated the role of Dicer1-dependent factors produced by the proximal epididymis (initial segment/caput)- including miRNAs- on the regulation of epididymal gene expression in the distal epididymis regions (i...
2016: PloS One
Franceli Rodrigues Kulcheski, Ana Paula Christoff, Rogerio Margis
Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that are involved in transcriptional and posttranscriptional gene expression regulation. The development of deep sequencing of ribosomal RNA (rRNA)-depleted RNA libraries, associated with improved computational tools, has provided the identification of several new circRNAs in all sorts of organisms, from protists, plants and fungi to animals. Recently, it was discovered that endogenous circRNAs can work as microRNA (miRNA) sponges. This means that the circRNAs bind to miRNAs and consequently repress their function, providing a new model of action for this class of ncRNA, as well as indicating another mechanism that regulates miRNA activity...
November 20, 2016: Journal of Biotechnology
Tomohito Yamasaki, Masayuki Onishi, Eun-Jeong Kim, Heriberto Cerutti, Takeshi Ohama
Canonical microRNAs (miRNAs) are embedded in duplexed stem-loops in long precursor transcripts and are excised by sequential cleavage by DICER nuclease(s). In this miRNA biogenesis pathway, dsRNA-binding proteins play important roles in animals and plants by assisting DICER. However, these RNA-binding proteins are poorly characterized in unicellular organisms. Here we report that a unique RNA-binding protein, Dull slicer-16 (DUS16), plays an essential role in processing of primary-miRNA (pri-miRNA) transcripts in the unicellular green alga Chlamydomonas reinhardtii In animals and plants, dsRNA-binding proteins involved in miRNA biogenesis harbor two or three dsRNA-binding domains (dsRBDs), whereas DUS16 contains one dsRBD and also an ssRNA-binding domain (RRM)...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
Chaoxia Zou, Chendan Zou, Wanpeng Cheng, Qiang Li, Zhongjing Han, Xiaona Wang, Jianfeng Jin, Jiaqi Zou, Zhiyan Liu, Zhongqiu Zhou, Weiming Zhao, Zhimin Du
Heme metabolism system is involved in microRNA (miRNA) biogenesis. The complicated interplay between heme oxygenase-1 (HO-1) and miRNA has been observed in various tissues and diseases, including human malignancy. In the present study, our data showed that stable HO-1 overexpression in hepatocellular carcinoma (HCC) cells downregulated several oncomiRs. The most stably downregulated are miR-30d and miR-107. Iron, one of HO-1 catalytic products, was an important mediator in this regulation. Cell function analysis demonstrated that HO-1 inhibited the proliferation and metastasis of HepG2 cells, whereas miR-30d/miR-107 improved the proliferative and migratory ability of HepG2 cells...
August 30, 2016: Oncology Reports
Masaru Yoshikawa, Yoichi Robertus Fujii
Dysfunction of ribosome biogenesis induces divergent ribosome-related diseases including ribosomopathy and occasionally results in carcinogenesis. Although many defects in ribosome-related genes have been investigated, little is known about contribution of ribosomal RNA (rRNA) in ribosome-related disorders. Meanwhile, microRNA (miRNA), an important regulator of gene expression, is derived from both coding and noncoding region of the genome and is implicated in various diseases. Therefore, we performed in silico analyses using M-fold, TargetScan, GeneCoDia3, and so forth to investigate RNA relationships between rRNA and miRNA against cellular stresses...
2016: BioMed Research International
Ram Babu Undi, Usha Gutti, Ravi Kumar Gutti
BACKGROUND: Megakaryocytes (MKs), a rare population of bone marrow cells, are responsible for the production of platelets. Sick neonates are predisposed to developing thrombocytopenia (platelet count <150×109/L) and neonates are affected by several megakaryocyte disorders as compared to adults. HYPOTHESIS: MicroRNAs (miRNAs) have been shown to crucially involve in the regulation of stem-cell differentiation in normal as well as malignant hematopoiesis, but their role in regulation of biological differences between adult and neonatal megakaryopoiesis is unknown...
October 2016: International Journal of Biochemistry & Cell Biology
Chatla Srinivas, V Swathi, C Priyanka, T Anjana Devi, B V Subba Reddy, M Janaki Ramaiah, Utpal Bhadra, Manika Pal Bhadra
In eukaryotes, transcriptional regulation occurs via chromatin remodeling, mainly through post translational modifications of histones that package DNA into structural units. Histone deacetylases (HDACs) are enzymes that play important role in various biological processes by repressing gene expression. Suberoylanilide hydroxamic acid (SAHA) is a known HDAC inhibitor that showed significant anti cancer activity by relieving gene silencing against hematologic and solid tumors. We have designed and synthesized a series of SAHA analogs C1-C4 and performed biological studies to elucidate its anti-cancer effects...
November 2016: Apoptosis: An International Journal on Programmed Cell Death
Stéphane Flamant, Radia Tamarat
This article reviews our current knowledge about cell-derived extracellular vesicles (EVs), including microparticles and exosomes, and their emergence as mediators of a new important mechanism of cell-to-cell communication. Particular emphasis has been given to the increasing involvement of EVs in the field of radiation-induced vascular injury. Although EVs have been considered for a long time as cell "dust", they in fact precisely reflect the physiological state of the cells. The role of microparticles and exosomes in mediating vascular dysfunction suggests that they may represent novel pathways in short- or long-distance paracrine intercellular signaling in vascular environment...
August 2016: Radiation Research
Yiannis A Savva, Ali Rezaei, Georges St Laurent, Robert A Reenan
Transcription of genetic information from archival DNA into RNA molecule working copies is vital for proper cellular function and is highly accurate. In turn, RNAs serve structural, enzymatic, and regulatory roles, as well as being informational templates for the ribosomal translation of proteins. Following RNA synthesis, maturing of RNA molecules occurs through various RNA processing events. One component of the collection of processes involving RNA species, broadly defined as RNA metabolism, is the RNA-editing pathway and is found in all animals...
2016: Frontiers in Genetics
Janis Kruse, Doreen Meier, Fides Zenk, Maren Rehders, Wolfgang Nellen, Christian Hammann
The maturation pathways of microRNAs (miRNAs) have been delineated for plants and several animals, belonging to the evolutionary supergroups of Archaeplastida and Opisthokonta, respectively. Recently, we reported the discovery of the microprocessor complex in Dictyostelium discoideum of the Amoebozoa supergroup. The complex is composed of the Dicer DrnB and the dsRBD (double-stranded RNA binding domain) containing protein RbdB. Both proteins localize at nucleoli, where they physically interact, and both are required for miRNA maturation...
July 14, 2016: RNA Biology
Matthew J Warner, Katherine S Bridge, James P Hewitson, Michael R Hodgkinson, Alex Heyam, Bailey C Massa, Jessica C Haslam, Maria Chatzifrangkeskou, Gareth J O Evans, Michael J Plevin, Tyson V Sharp, Dimitris Lagos
MicroRNAs (miRNAs) are short non-coding RNAs that silence mRNAs. They are generated following transcription and cleavage by the DROSHA/DGCR8 and DICER/TRBP/PACT complexes. Although it is known that components of the miRNA biogenesis machinery can be phosphorylated, it remains poorly understood how these events become engaged during physiological cellular activation. We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells...
July 12, 2016: Nucleic Acids Research
Daniele Hasler, Gunter Meister
Although RNA are synthesized as single-stranded molecules, most of them are characterized by extensive secondary structures. Two RNA that require distinct folding for biogenesis and function are miRNA and tRNA. While miRNA are processed from hairpin-containing precursors, tRNA are folded into characteristic L-shaped structures. In addition, tRNA and their precursors are a rich source of RNA fragments. Recent findings suggest that their production might be determined by structural characteristics of the tRNA substrates...
August 2016: FEBS Letters
Frank Qian, Ye Feng, Yonglan Zheng, Temidayo O Ogundiran, Oladosu Ojengbede, Wei Zheng, William Blot, Christine B Ambrosone, Esther M John, Leslie Bernstein, Jennifer J Hu, Regina G Ziegler, Sarah Nyante, Elisa V Bandera, Sue A Ingles, Michael F Press, Katherine L Nathanson, Anselm Hennis, Barbara Nemesure, Stefan Ambs, Laurence N Kolonel, Olufunmilayo I Olopade, Christopher A Haiman, Dezheng Huo
MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry...
October 2016: Human Genetics
Behrooz Darbani, Shahin Noeparvar, Søren Borg
RNA circularization made by head-to-tail back-splicing events is involved in the regulation of gene expression from transcriptional to post-translational levels. By exploiting RNA-Seq data and down-stream analysis, we shed light on the importance of circular RNAs in plants. The results introduce circular RNAs as novel interactors in the regulation of gene expression in plants and imply the comprehensiveness of this regulatory pathway by identifying circular RNAs for a diverse set of genes. These genes are involved in several aspects of cellular metabolism as hormonal signaling, intracellular protein sorting, carbohydrate metabolism and cell-wall biogenesis, respiration, amino acid biosynthesis, transcription and translation, and protein ubiquitination...
2016: Frontiers in Plant Science
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