Abstract:
:Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-glycine-glycine (RGG) box. However, several properties of the FMRP amino terminus are unresolved. It has been documented for over a decade that the amino terminus has the ability to bind RNA despite having no recognizable functional motifs. Moreover, the amino terminus has recently been shown to bind chromatin and influence the DNA damage response as well as function in the presynaptic space, modulating action potential duration. We report here the amino terminal crystal structures of wild-type FMRP, and a mutant (R138Q) that disrupts the amino terminus function, containing an integral tandem Agenet and discover a novel KH motif.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Myrick LK,Hashimoto H,Cheng X,Warren STdoi
10.1093/hmg/ddu586subject
Has Abstractpub_date
2015-03-15 00:00:00pages
1733-40issue
6eissn
0964-6906issn
1460-2083pii
ddu586journal_volume
24pub_type
杂志文章abstract::Spliceosomal Uridine-rich small ribonucleo protein (U snRNP) assembly is an active process mediated by the macromolecular survival motor neuron (SMN) complex. This complex contains the SMN protein and six additional proteins, named Gemin2-7, according to their localization to nuclear structures termed gems. Here, we p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi343
更新日期:2005-10-15 00:00:00
abstract::Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmed or stochastic nature of hypomethylation, identifying these changes is important in understanding v...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt365
更新日期:2013-12-20 00:00:00
abstract::Degenerate primer pairs that include consensus sequences of evolutionary conserved portions of protein families (BLOCKs or ancient conserved regions) can be used to screen by polymerase chain reaction (PCR) for cognate cDNAs and YACs through much of phylogeny. Nine such primer pairs were developed, and five with sites...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.5.735
更新日期:1994-05-01 00:00:00
abstract::The molecular mechanisms regulating expression of utrophin A are of therapeutic interest since upregulating its expression at the sarcolemma can compensate for the lack of dystrophin in animal models of Duchenne Muscular Dystrophy (DMD). The 5'-UTR of utrophin A has been previously shown to drive cap-independent inter...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp591
更新日期:2010-04-01 00:00:00
abstract::Integrating single-cell RNA sequencing (scRNA-seq) data with genotypes obtained from DNA sequencing studies facilitates the detection of functional genetic variants underlying cell type-specific gene expression variation. Unfortunately, most existing scRNA-seq studies do not come with DNA sequencing data; thus, being ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz207
更新日期:2019-11-01 00:00:00
abstract::We introduced a targeted single base deletion at codon 307 of the rds-peripherin gene in mice, similar mutations being known to cause autosomal dominant retinitis pigmentosa (RP) in man. Histopathological and electroretinographic analysis indicate that the retinopathy in mice homozygous for the codon 307 mutation appe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.9.1005
更新日期:2002-05-01 00:00:00
abstract::Germline mutations in LKB1 have been reported to underlie familial Peutz-Jeghers syndrome (PJS) with intestinal hamartomatous polyps and an elevated risk of various neoplasms. To investigate the prevalence of LKB1 germline mutations in PJS more generally, we studied samples from 33 unrelated PJS patients including eig...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.1.45
更新日期:1999-01-01 00:00:00
abstract::The gene which is defective in Duchenne muscular dystrophy (DMD) is the largest known gene. The product of the gene in muscle, dystrophin, is a 427 kDa protein. The same gene encodes at least six additional products: two non-muscle dystrophin isoforms transcribed from promoters located in the 5'-end region of the gene...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.4.581
更新日期:1998-04-01 00:00:00
abstract::Synapsin I (SynI) is a synaptic vesicle (SV) phosphoprotein playing multiple roles in synaptic transmission and plasticity by differentially affecting crucial steps of SV trafficking in excitatory and inhibitory synapses. SynI knockout (KO) mice are epileptic, and nonsense and missense mutations in the human SYN1 gene...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt071
更新日期:2013-06-01 00:00:00
abstract::Many congenital myasthenic syndromes (CMS) are associated with mutations in the genes encoding the acetylcholine receptor (AChR), an oligomeric protein with the structure alpha(2)betadelta epsilon. AChR deficiency is frequently due to homozygous or heteroallelic mutations in the AChR epsilon subunit, most of which cau...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.24.3087
更新日期:2002-11-15 00:00:00
abstract::P-selectin is an adhesion molecule, expressed at the surface of activated cells, that mediates the interaction of activated endothelial cells or platelets with leukocytes. P-selectin expression is increased in atherosclerotic plaques, and high plasma levels of this molecule have been observed in patients with unstable...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.8.1277
更新日期:1998-08-01 00:00:00
abstract::Pseudoachondroplasia (PSACH) is one of the more common skeletal dysplasias and results from mutations in cartilage oligomeric matrix protein (COMP). Most COMP mutations identified to date cluster in the TSP3 repeat region of COMP and the mutant protein is retained in the rough endoplasmic reticulum (rER) of chondrocyt...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm155
更新日期:2007-09-01 00:00:00
abstract::The FUS gene at 16p11 fuses with DDIT3 and ATF1 as the result of translocations with chromosome band 12q13 in myxoid liposarcoma and angiomatoid fibrous histiocytoma, respectively, and with ERG as the result of a t(16;21)(p11;q22) in acute myeloid leukemia. We here show that a t(7;16)(q33;p11) in two cases of low grad...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg237
更新日期:2003-09-15 00:00:00
abstract::A gene's transcriptional output is the combined product of two inputs: diffusible factors in the cellular milieu acting in trans, and chromatin state acting in cis. Here, we describe a strategy for dissecting the relative contribution of cis versus trans mechanisms to gene regulation. Referred to as trans complementat...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn409
更新日期:2009-03-01 00:00:00
abstract::A functional genetic screen using loss-of-function and gain-of-function alleles was performed to identify modifiers of tau-induced neurotoxicity using the 2N/4R (full-length) isoform of wild-type human tau expressed in the fly retina. We previously reported eye pigment mutations, which create dysfunctional lysosomes, ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr432
更新日期:2011-12-15 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::Defects in FAM161A, a protein of unknown function localized at the cilium of retinal photoreceptor cells, cause retinitis pigmentosa, a form of hereditary blindness. By using different fragments of this protein as baits to screen cDNA libraries of human and bovine retinas, we defined a yeast two-hybrid-based FAM161A i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv085
更新日期:2015-06-15 00:00:00
abstract::Recent studies with tiling arrays have revealed more genomic transcription than previously anticipated. Whole new groups of non-coding transcripts (NCTs) have been detected. Some of these NCTs, including miRNAs, can regulate gene expression. To date, most known NCTs studied have been relatively short, but several impo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm336
更新日期:2008-03-01 00:00:00
abstract::Meningiomas are common nervous system tumors, whose molecular pathogenesis is poorly understood. To date, the most frequent genetic alteration detected in these tumors is loss of heterozygosity (LOH) on chromosome 22q. This finding led to the identification of the neurofibromatosis 2 (NF2) tumor suppressor gene on 22q...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.10.1495
更新日期:2000-06-12 00:00:00
abstract::Peroxisomes are vital eukaryotic organelles that participate in lipid metabolism, in particular the metabolism of very-long-chain fatty acids (VLCFA). The biogenesis of peroxisomes is regulated by a set of peroxin proteins (PEX). In humans, mutations affecting peroxin protein production or function result in devastati...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp518
更新日期:2010-02-01 00:00:00
abstract::Microsatellite instability (MSI) characterizes tumors arising in patients with hereditary non-polyposis colorectal cancer (HNPCC) syndrome. HNPCC is a hereditary autosomal dominant disease caused by germline mutations in genes from the DNA (MMR) mismatch repair system. In these tumors, the loss of MMR compromises the ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi021
更新日期:2005-01-15 00:00:00
abstract::Obesity is a major public health problem with strong genetic determination; however, the genetic factors underlying obesity are largely unknown. In this study, we performed a genome-wide association scan for obesity by examining approximately 500 000 single-nucleotide polymorphisms (SNPs) in a sample of 1000 unrelated...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn072
更新日期:2008-06-15 00:00:00
abstract::Hirschsprung disease (HSCR) is a frequent neurocristopathy characterized by the absence of submucosal and myenteric plexuses in a variable length of the gastrointestinal tract. Pedigrees and segregation analyses suggested the involvement of one or several dominant genes with low penetrance in HSCR. Considering that RE...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.9.1449
更新日期:1998-09-01 00:00:00
abstract::A single-base substitution in the coding region of the androgen receptor (AR) gene caused complete androgen insensitivity in a patient with 46,XY karyotype. The mutation was a T-to-G transition in exon 6 and changed the codon 807 from ATG (methionine) to AGG (arginine) in the hormone-binding domain of the protein. The...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.11.1809
更新日期:1993-11-01 00:00:00
abstract::Ciliopathies form a group of inherited disorders sharing several clinical manifestations because of abnormal cilia formation or function, and few treatments have been successful against these disorders. Here, we report a mouse model with mutated Sclt1 gene, which encodes a centriole distal appendage protein important ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx183
更新日期:2017-08-01 00:00:00
abstract::Fanconi anaemia (FA) is an autosomal recessive genetic disorder characterized by progressive bone marrow failure, multiple congenital abnormalities, and an increased risk of cancer. FA cells are characterized by chromosomal instability and hypersensitivity to DNA interstrand crosslinking agents. At least eight complem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg266
更新日期:2003-10-01 00:00:00
abstract::Slow channel congenital myasthenic syndrome (SCCMS) is a disorder of the neuromuscular synapse caused by dominantly inherited missense mutations in genes that encode the muscle acetylcholine receptor (AChR) subunits. Here we investigate the potential of post-transcriptional gene silencing using RNA interference (RNAi)...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg280
更新日期:2003-10-15 00:00:00
abstract::We previously showed that disruptive complex I mutations in mitochondrial DNA are the main genetic hallmark of oncocytic tumors of the thyroid and kidney. We here report a high frequency of homoplasmic disruptive mutations in a large panel of oncocytic pituitary and head-and-neck tumors. The presence of such mutations...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp566
更新日期:2010-03-15 00:00:00
abstract::Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, 5-10% of healthy adults fail to produce protective levels of antibody against the hepatitis B vaccination. It has been reported that host genetic variants might affect the immune response to hepatitis B vacc...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt586
更新日期:2014-04-15 00:00:00
abstract::The clinical manifestations of inherited neurodegenerative diseases are often delayed for periods from years to decades. This observation has led to the idea that, in these disorders, neurons die from cumulative damage. A critical prediction of the cumulative damage hypothesis is that the probability of neuronal death...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/10.20.2269
更新日期:2001-10-01 00:00:00