Abstract:
:One mechanism by which endogenous microRNAs (miRNAs) function is to suppress translation of target mRNAs. Computational identification of target mRNAs is hampered by the partial complementarity between miRNAs and their targets and the lack of in vivo approaches to identify targets. Here, we identify mRNAs that are regulated by specific endogenous miRNA by detecting shifts in individual mRNA abundance in polyribosome profiles following miRNA knockdown via siRNA. We have identified human genes whose mRNAs were found at significantly increased levels in the heavy polyribosome fractions following miRNA miR-30a-3p knockdown. If antibody was available, targets showed an increase in protein levels following the miRNA knockdown and a decrease following the miRNA overexpression. Although all identified transcripts have sequences that partially complement miR-30a-3p, none was identified by commonly used computational means. These data suggest that the functional interaction between miRNAs and mRNA targets is more complex than previously realized and describe an approach to refine predictive algorithms.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Nakamoto M,Jin P,O'Donnell WT,Warren STdoi
10.1093/hmg/ddi397subject
Has Abstractpub_date
2005-12-15 00:00:00pages
3813-21issue
24eissn
0964-6906issn
1460-2083pii
ddi397journal_volume
14pub_type
杂志文章abstract::Genetic studies have implicated the neuronal ubiquitin C-terminal hydrolase (UCH) protein UCH-L1 in Parkinson's disease (PD) pathogenesis. Moreover, the function of UCH-L1 may be lost in the brains of PD and Alzheimer's disease patients. We have previously reported that the UCH-L1 polymorphic variant S18Y, potentially...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr521
更新日期:2012-02-15 00:00:00
abstract::GM2 gangliosidoses are a group of lysosomal storage disorders which include Sandhoff disease and Tay-Sachs disease. Dysregulation of glutamate receptors has been recently postulated in the pathology of Sandhoff disease. Glutamate receptor association with neuronal pentraxins 1 and 2, and the neuronal pentraxin recepto...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw422
更新日期:2017-02-15 00:00:00
abstract::To further identify novel susceptibility loci of nasopharyngeal carcinoma (NPC), we here extended our previous genome-wide association study (GWAS) by boosting statistical power with larger sample size and validating more SNPs in the ranking list based on the GWAS P-values. The discovery stage consisting of 463,250 SN...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw200
更新日期:2016-08-15 00:00:00
abstract::FMR1 protein expression was studied in different tissues. In human, monkey and murine tissues, high molecular mass FMR1 proteins (67-80 kDa) are found, as shown in lymphoblastoid cells lines. The identity of these proteins was confirmed by their absence in tissues from patients with the fragile X syndrome and a FMR1 k...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.5.895
更新日期:1995-05-01 00:00:00
abstract::Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 (NRG1) type III regulate Schwann cell fate and myelination. Here we ask if modulating NRG1 type III le...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy420
更新日期:2019-04-15 00:00:00
abstract::In the field of muscular dystrophy, advances in understanding the molecular basis of the various disorders in this group have been rapidly translated into readily applicable diagnostic tests, allowing the provision of more accurate prognostic and genetic counselling. The limb-girdle muscular dystrophies (LGMD) have re...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/8.10.1875
更新日期:1999-01-01 00:00:00
abstract::Germline mutations in the RB1 gene confer hereditary predisposition to retinoblastoma. The majority of these mutations occur de novo and differ from one patient to another. Cytogenetics and Southern blotting were shown to detect less than 15% of constitutional rearrangements. In this study we used the polymerase chain...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.7.975
更新日期:1993-07-01 00:00:00
abstract::Mitochondrial dysfunction plays an important role in the etiology of neurodegenerative diseases. However, the progressive nature of neuronal loss in genetic models of mitochondrial dysfunction suggests the presence of compensatory mechanisms promoting neuronal survival under these conditions. Here, we identified the e...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds500
更新日期:2013-03-01 00:00:00
abstract::Schizophrenia may arise from subtle abnormalities in brain development due to alterations in the functions of candidate susceptibility genes such as Disrupted-in-schizophrenia 1 (DISC1) and Neuregulin 1 (NRG1). To provide novel insights into the functions of DISC1 in brain development, we mapped the expression of zebr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn361
更新日期:2009-02-01 00:00:00
abstract::Metabolic control of phenylalanine concentrations in body fluids is essential for cognitive development and executive function. The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy079
更新日期:2018-05-15 00:00:00
abstract::Schwann cells are the myelinating glia of the peripheral nervous system and dysfunction of these cells causes motor and sensory peripheral neuropathy. The transcription factor SOX10 is critical for Schwann cell development and maintenance, and many SOX10 target genes encode proteins required for Schwann cell function....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw233
更新日期:2016-09-15 00:00:00
abstract::ICF syndrome has been described as the association of variable immunodeficiency, facial anomalies and centromeric heterochromatin instability. Since the chromosome rearrangements seen in cells of ICF patients are reminiscent of the chromosomal changes induced by the undermethylating agent 5-azacytidine in the late S-p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.6.731
更新日期:1993-06-01 00:00:00
abstract::Protein engineering is a means to optimize protein therapeutics developed for the treatment of so far incurable diseases including cancers and genetic disorders. Here we report on an engineering approach in which we successfully increased the catalytic rate constant of an enzyme that is presently evaluated in enzyme r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz020
更新日期:2019-06-01 00:00:00
abstract::Chromosomal common fragile sites (CFSs) are genetically unstable regions of the genome that are induced by conditions that impair DNA replication. In this report, we show that treatment with the DNA polymerase inhibitor, aphidicolin (APH), slows the replication rate throughout S phase. To investigate the unusual sensi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp470
更新日期:2010-01-01 00:00:00
abstract::Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE le...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.1.27
更新日期:1998-01-01 00:00:00
abstract::PTEN, a tumor suppressor phosphatase that dephosphorylates both protein and lipid substrates, is mutated in both heritable and sporadic breast cancer. Until recently, PTEN-mediated cell cycle arrest and apoptosis were thought to occur through its well-documented cytoplasmic activities. We have shown that PTEN localize...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl177
更新日期:2006-09-01 00:00:00
abstract::Expanded glutamine repeats of the ataxin-2 (ATXN2) protein cause spinocerebellar ataxia type 2 (SCA2), a rare neurodegenerative disorder. More recent studies have suggested that expanded ATXN2 repeats are a genetic risk factor for amyotrophic lateral sclerosis (ALS) via an RNA-dependent interaction with TDP-43. Given ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr227
更新日期:2011-08-15 00:00:00
abstract::Gene therapy holds great promise for curing Duchenne muscular dystrophy (DMD), the most common fatal inherited childhood muscle disease. Success of DMD gene therapy depends upon functional improvement in both skeletal and cardiac muscle. Numerous gene transfer studies have been performed to correct skeletal muscle pat...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh174
更新日期:2004-08-01 00:00:00
abstract::Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder and a leading genetic cause of infantile mortality. SMA is caused by mutation or deletion of Survival Motor Neuron-1 (SMN1). The clinical features of the disease are caused by specific degeneration of alpha-motor neurons in the spinal c...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddq147
更新日期:2010-04-15 00:00:00
abstract::Beside the well-known polyglutamine expansions involved in several neurodegenerative disorders, convergent recent findings pointed to the expansion of polyalanine stretches as a disease mechanism in congenital malformations, skeletal dysplasia and nervous system anomalies. Polyalanine stretches have been predicted in ...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddh251
更新日期:2004-10-01 00:00:00
abstract::Niemann-Pick type C (NPC) disease, an autosomal recessive disorder caused primarily by loss-of-function mutations in NPC1 gene, is characterized neuropathologically by intracellular cholesterol accumulation, gliosis and neuronal loss in selected brain regions. Recent studies have shown that NPC disease exhibits intrig...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds322
更新日期:2012-11-15 00:00:00
abstract::Disruption of the blood-brain barrier (BBB) is a serious complication frequently encountered in neurodegenerative disorders. Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. It remains u...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds038
更新日期:2012-05-15 00:00:00
abstract::Following a screen for neuromuscular mouse mutants, we identified ostes, a novel N-ethyl N-nitrosourea-induced mouse mutant with muscle atrophy. Genetic and biochemical evidence shows that upregulation of the novel, uncharacterized transient receptor potential polycystic (TRPP) channel PKD1L2 (polycystic kidney diseas...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp304
更新日期:2009-10-01 00:00:00
abstract::Genome-wide scans for linkage of chromosome regions to type 1 diabetes in affected sib pair families have revealed that the major susceptibility locus resides within the major histocompatibility complex (MHC) on chromosome 6p21 (lambda S = 2.4). It is recognized that the MHC contains multiple susceptibility loci (refe...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/5.supplement_1.1443
更新日期:1996-01-01 00:00:00
abstract::The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca(2+) o) homeos...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv226
更新日期:2015-09-15 00:00:00
abstract::We performed a molecular study with 21 microsatellites on a sample of 82 trisomy 13 conceptuses, the largest number of cases studied to date. The parental origin was determined in every case and in 89% the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII errors. The latter ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm148
更新日期:2007-08-15 00:00:00
abstract::Even though autoimmune diseases are heterogeneous, believed to result from the interaction between genetic and environmental components, patients with these disorders exhibit reproducible patterns of gene expression in their peripheral blood mononuclear cells. A portion of this gene expression profile is a property of...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi466
更新日期:2006-02-01 00:00:00
abstract::Galphaq, encoded by the human GNAQ gene, is an effector subunit of the Gq heterotrimeric G-protein and the convergence point for signaling of multiple Gq-coupled neurohormonal receptors. To identify naturally occurring mutations that could modify GNAQ transcription, we examined genomic DNA isolated from 355 normal sub...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm229
更新日期:2007-11-15 00:00:00
abstract::Imputation is commonly used in genome-wide association studies to expand the set of genetic variants available for analysis. Larger and more diverse reference panels, such as the final Phase 3 of the 1000 Genomes Project, hold promise for improving imputation accuracy in genetically diverse populations such as Hispani...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw174
更新日期:2016-08-01 00:00:00
abstract::Osteoarthritis (OA) is a common, multifactorial and polygenic skeletal disease that, in its severest form, requires joint replacement surgery to restore mobility and to relieve chronic pain. Using tissues from the articulating joints of 260 patients with OA and a range of in vitro experiments, including CRISPR-Cas9, w...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy257
更新日期:2018-10-01 00:00:00