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Yuri Pekarsky, Veronica Balatti, Alexey Palamarchuk, Lara Rizzotto, Dario Veneziano, Giovanni Nigita, Laura Z Rassenti, Harvey I Pass, Thomas J Kipps, Chang-Gong Liu, Carlo M Croce
Chronic lymphocytic leukemia (CLL) is the most common human leukemia, and transgenic mouse studies indicate that activation of the T-cell leukemia/lymphoma 1 (TCL1) oncogene is a contributing event in the pathogenesis of the aggressive form of this disease. While studying the regulation of TCL1 expression, we identified the microRNA cluster miR-4521/3676 and discovered that these two microRNAs are associated with tRNA sequences and that this region can produce two small RNAs, members of a recently identified class of small noncoding RNAs, tRNA-derived small RNAs (tsRNAs)...
May 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
Qi Chen, Menghong Yan, Zhonghong Cao, Xin Li, Yunfang Zhang, Junchao Shi, Gui-hai Feng, Hongying Peng, Xudong Zhang, Ying Zhang, Jingjing Qian, Enkui Duan, Qiwei Zhai, Qi Zhou
Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions...
January 22, 2016: Science
Maria R Garcia-Silva, Roberta Ferreira Cura das Neves, Florencia Cabrera-Cabrera, Julia Sanguinetti, Lia C Medeiros, Carlos Robello, Hugo Naya, Tamara Fernandez-Calero, Thais Souto-Padron, Wanderley de Souza, Alfonso Cayota
The protozoan parasite Trypanosoma cruzi has a complex life cycle characterized by intracellular and extracellular forms alternating between invertebrate and mammals. To cope with these changing environments, T. cruzi undergoes rapid changes in gene expression, which are achieved essentially at the posttranscriptional level. At present, expanding families of small RNAs are recognized as key players in novel forms of posttranscriptional gene regulation in most eukaryotes. However, T. cruzi lacks canonical small RNA pathways...
January 2014: Parasitology Research
Monir Shababi, Jacqueline Glascock, Christian L Lorson
Spinal muscular atrophy (SMA), a neurodegenerative disease, is the second most common genetic disorder and the leading genetic cause of infantile death. SMA arises from the loss of Survival Motor Neuron-1 (SMN1), leading to degeneration of lower motor neurons and, consequently, the atrophy of voluntary muscles. A duplicated copy gene called SMN2 exists in humans. SMN2 is unable to fully compensate for the loss of SMN1 because it produces very low levels of functional SMN protein due to an alternative splicing event...
February 2011: Human Gene Therapy
Dirk Haussecker, Yong Huang, Ashley Lau, Poornima Parameswaran, Andrew Z Fire, Mark A Kay
Competition between mammalian RNAi-related gene silencing pathways is well documented. It is therefore important to identify all classes of small RNAs to determine their relationship with RNAi and how they affect each other functionally. Here, we identify two types of 5'-phosphate, 3'-hydroxylated human tRNA-derived small RNAs (tsRNAs). tsRNAs differ from microRNAs in being essentially restricted to the cytoplasm and in associating with Argonaute proteins, but not MOV10. The first type belongs to a previously predicted Dicer-dependent class of small RNAs that we find can modestly down-regulate target genes in trans...
April 2010: RNA
Tristan H Coady, Travis D Baughan, Monir Shababi, Marco A Passini, Christian L Lorson
RNA modalities are developing as a powerful means to re-direct pathogenic pre-mRNA splicing events. Improving the efficiency of these molecules in vivo is critical as they move towards clinical applications. Spinal muscular atrophy (SMA) is caused by loss of SMN1. A nearly identical copy gene called SMN2 produces low levels of functional protein due to alternative splicing. We previously reported a trans-splicing RNA (tsRNA) that re-directed SMN2 splicing. Now we show that reducing the competition between endogenous splices sites enhanced the efficiency of trans-splicing...
2008: PloS One
V I Agol, S G Drozdov, M P Frolova, V P Grachev, M S Kolesnikova, V G Kozlov, N M Ralph, L I Romanova, E A Tolskaya, E G Viktorova
A tsRNA- intertypic recombinant, v3/a1-25, which has the 5' and 3' halves of the genome derived from the neurovirulent type 3 poliovirus strain 452/62 3D and the attenuated type 1 poliovirus strain LSc-gr3, respectively, was previously shown to cause severe paralytic poliomyelitis after intracerebral inoculation of monkeys. To ascertain whether the illness was caused by the recombinant itself or by temperature-resistant trRNA+ mutants that might have arisen in the inoculated monkeys, five independent virus strains have been isolated from the spinal cord of the diseased animals...
February 1985: Journal of General Virology
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