Abstract:
:We had previously proposed that the post-transcriptional regulation through microRNA as a mechanism for incomplete penetrance and variable expressivity, leads to lack of correlation between genotype and phenotype. Here we report the validation of miRNA-target interactions we predicted earlier and demonstrate the regulation of endogenous JAG1 by hsa-miR-214 and hsa-miR-124, and TGFBR2 by hsa-miR-34b*, through luciferase activity of reporter constructs and also the expression levels of the endogenous genes. Using these targets, we have modeled the diploid state for miRNA target site with heterozygosity for the SNP and demonstrate the differential targeting of an otherwise identical 3'UTR. We show that SNP rs8708 (A > G) at the target site of hsa-miR-214 can relieve the repression while an SNP rs11466532 (C > T) enhances the repression of reporter expression by hsa-miR-34b*. We discuss the results in the light of its implications in the context of penetrance of dominant mutations in miRNA targeted genes, using JAG1 as an example. These observations imply that disease causing mutations in JAG1 linked to the SNP rs8708G will be poorly targeted by hsa-miR-214 when present against a normal allele of JAG1 with rs8708A and will show penetrance of JAG1 mutations as Alagille syndrome, while mutant JAG1 linked to rs8708A against rs8708G on the normal allele will show either no disease or much attenuated symptoms and hence exhibit incomplete penetrance.
journal_name
RNA Bioljournal_title
RNA biologyauthors
Ahluwalia JK,Soni K,Sivasubbu S,Brahmachari Vdoi
10.4161/rna.19318subject
Has Abstractpub_date
2012-03-01 00:00:00pages
351-60issue
3eissn
1547-6286issn
1555-8584pii
19318journal_volume
9pub_type
杂志文章相关文献
RNA Biology文献大全abstract::Heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a multifunctional RNA-binding protein that is involved in many different processes, such as regulation of transcription, translation, and RNA stability. We have previously characterized hnRNP L as a global regulator of alternative splicing, binding to CA-repeat, a...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.27991
更新日期:2014-01-01 00:00:00
abstract::Deinococcus radiodurans is a highly stress resistant bacterium that encodes universal as well as lineage-specific factors involved in DNA transcription and repair. However, the effects of DNA lesions on RNA synthesis by D. radiodurans RNA polymerase (RNAP) have never been studied. We investigated the ability of this R...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1656027
更新日期:2019-12-01 00:00:00
abstract::Contributions of dietary miRNAs to circulating small RNA profiles would have profound implications for interpretation of miRNA biomarker studies: presumptive disease-specific markers might instead indicate responses to disease-associated quantitative or qualitative dietary alteration. This examination weighs the evide...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.21619
更新日期:2012-09-01 00:00:00
abstract::Selenoproteins are a unique class of proteins that contain the 21st amino acid, selenocysteine (Sec). Addition of Sec into a protein is achieved by recoding of the UGA stop codon. All 25 mammalian selenoprotein mRNAs possess a 3' UTR stem-loop structure, the Selenocysteine Insertion Sequence (SECIS), which is required...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1653681
更新日期:2019-12-01 00:00:00
abstract::Two different isolates of the myxomycete Didymium iridis harbour homing endonuclease genes that are expressed from group I introns inserted into identical sites within the small subunit ribosomal DNA. The homing endonuclease proteins are related in sequence, and their gene structures share similar features such as the...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.3.4.3958
更新日期:2006-10-01 00:00:00
abstract::MicroRNAs (miRNAs) are a class of small noncoding RNAs about 22-nucleotide (nt) in length that collectively regulate more than 60% of coding genes. Aberrant miRNA expression is associated with numerous diseases, including cancer. miRNA biogenesis is licenced by the ribonuclease (RNase) III enzyme Drosha, the regulatio...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1813439
更新日期:2020-11-01 00:00:00
abstract::MicroRNAs (miRNAs) are key regulators of gene expression and play critical roles in modulating metabolism, development and physiology in animals and plants. miRNA levels are transcriptionally and post-transcriptionally controlled for their proper function. Recent studies have shown that RNA-binding proteins play impor...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.22740
更新日期:2012-12-01 00:00:00
abstract::Alzheimer's disease (AD) has devastating consequences for patients during its slow, progressive course. It is important to understand the pathology of AD onset. Recently, circular RNAs (circRNAs) have been found to participate in many human diseases including cancers and neurodegenerative conditions. In this study, we...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1783487
更新日期:2020-12-01 00:00:00
abstract::Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In this study, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed 10 billion Illumina reads from 477 serum samples, inclu...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2017.1403003
更新日期:2018-02-01 00:00:00
abstract::Processing bodies (P-bodies) are cytoplasmatic mRNP granules containing non-translating mRNAs and proteins from the mRNA decay and silencing machineries. The mechanism of P-body assembly has been typically addressed by depleting P-body components. Here we apply a complementary approach and establish an automated cell-...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.26851
更新日期:2013-11-01 00:00:00
abstract::The NOVA (neuro-oncological ventral antigen) protein family, composed of two paralogs, NOVA1 and NOVA2, consists of RNA-binding proteins involving in processes such as alternative splicing and transport of some target mRNAs. The function of NOVA has been well studied, and increasing evidence has shown that NOVA protei...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1734372
更新日期:2020-06-01 00:00:00
abstract::The development of rigorous molecular taxonomy pioneered by Carl Woese has freed evolution science to explore numerous cellular activities that lead to genome change in evolution. These activities include symbiogenesis, inter- and intracellular horizontal DNA transfer, incorporation of DNA from infectious agents, and ...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.27506
更新日期:2014-01-01 00:00:00
abstract::microRNAs (miRNAs) are critical regulators of gene expression. For elucidating functional roles of miRNAs, it is critical to identify their direct targets. There are debates about whether pulldown of biotinylated miRNA mimics can be used to identify miRNA targets or not. Here we show that biotin-labelled miR-34a can b...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2017.1391441
更新日期:2018-01-02 00:00:00
abstract::Single-stranded oligonucleotides (ssOligos) are efficiently taken up by living cells without the use of transfection reagents. This phenomenon called 'gymnosis' enables the sequence-specific silencing of target genes in various types of cells. Several antisense ssOligos are used for the treatment of human diseases. Ho...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2017.1302641
更新日期:2017-11-02 00:00:00
abstract::Bacterial small RNAs (sRNAs) are a class of structural RNAs that often regulate mRNA targets via post-transcriptional base pair interactions. We determined features that discriminate functional from non-functional interactions and assessed the influence of these features on genome-wide target predictions. For this pur...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.20294
更新日期:2012-07-01 00:00:00
abstract::The tight gene expression regulation controls the development and pathogenesis of human malaria parasite Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1732032
更新日期:2020-06-01 00:00:00
abstract::By differential high-throughput RNA sequencing (dRNA-seq) we have identified "product RNAs" (pRNAs) as short as 8-12 nucleotides that are synthesized by Bacillus subtilis RNA polymerase (RNAP) in vivo using the regulatory 6S-1 RNA as template. The dRNA-seq data were confirmed by in vitro transcription experiments and ...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.8.5.16151
更新日期:2011-09-01 00:00:00
abstract::Many splicing regulators bind to their own pre-mRNAs to induce alternative splicing that leads to formation of unstable mRNA isoforms. This provides an autoregulatory feedback mechanism that regulates the cellular homeostasis of these factors. We have described such an autoregulatory mechanism for two core protein com...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2015.1096489
更新日期:2015-01-01 00:00:00
abstract::Traditionally the principles of protein folding in vivo have been obtained largely from molecular chaperone studies. Through extensive studies on molecular chaperones, it becomes clear that most proteins can fold without their assistance in vivo, suggesting the existence of other chaperone types and mechanisms. Since ...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.6.1.7441
更新日期:2009-01-01 00:00:00
abstract::Population bottlenecks often cause strong reductions in genetic diversity and alter population structure. In the context of host-parasite interactions, bottlenecks could in theory benefit either the host or the pathogen. We predicted that bottlenecking of bacterial populations that evolve CRISPR immunity against bacte...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1578608
更新日期:2019-04-01 00:00:00
abstract::The quaking viable (qk(v)) mice have attracted attention because of their characteristic tremor caused by their dysmyelination. In the central nervous system, qk(v) mice fail to develop mature myelinating oligodendrocytes and display uncompacted myelin. The genetic defect in the qk(v) mice prevents the proper expressi...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.2.2.1603
更新日期:2005-04-01 00:00:00
abstract::The PDCD1 gene encodes PD-1, an important immune checkpoint protein and key immunotherapy target to treat cancer. PDCD1 is alternatively spliced to generate an exon 3-skipped isoform PD-1Δ3 that has been suggested to play an antagonistic role to PD-1, but the mechanism underlying alternative splicing of PDCD1 has neve...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1659080
更新日期:2019-12-01 00:00:00
abstract::In eukaryotes and viruses that infect them, the 5' end of mRNA molecules, and also many other functionally important RNAs, are modified to form a so-called cap structure that is important for interactions of these RNAs with many nuclear and cytoplasmic proteins. The RNA cap has multiple roles in gene expression, inclu...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.1080/15476286.2015.1004955
更新日期:2014-01-01 00:00:00
abstract::RNA methylation, catalysed by a set of RNA methyltransferases (RNMTs), modulates RNA structures, properties, and biological functions. RNMTs are increasingly documented to be dysregulated in various human diseases, particularly developmental disorders and cancer. However, the genomic and transcriptomic alterations of ...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1708549
更新日期:2020-04-01 00:00:00
abstract::Amphioxus is the closest living proxy for exploring the evolutionary origin of the immune system in vertebrates. To understand the immune responses of amphioxus to lipopolysaccharide (LPS), 5 ribosomal RNA (rRNA)-depleted libraries of amphioxus were constructed, including one control (0 h) library and 4 treatment libr...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2017.1367890
更新日期:2017-12-02 00:00:00
abstract::Seryl-tRNA synthetase (SerRS) catalyzes the ligation of serine to the 3'-end of serine tRNA (tRNA(Ser)), which is typical of the type-2 tRNAs characterized by a long extra arm. The SerRSs are divided into two types, the archaeal/eukaryal and bacterial types. In this study, we solved the crystal structures of the SerRS...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.5.3.6876
更新日期:2008-07-01 00:00:00
abstract::The immaculate annotation of all microRNAs (miRNAs) is a prerequisite to study their biological function on a genome-wide scale. However, the original criteria for proper miRNA annotation seem unsuited for the automated analysis of the immense number of small RNA reads available in next generation sequencing (NGS) dat...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.8.3.14333
更新日期:2011-05-01 00:00:00
abstract::Riboswitches are cis-encoded, cis-acting RNA elements that directly sense a physiological signal. Signal response results in a change in RNA structure that impacts gene expression. Elements of this type play an important role in bacteria, where they regulate a variety of fundamental cellular pathways. Riboswitch-media...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.7.1.10757
更新日期:2010-01-01 00:00:00
abstract::"What does one do when the giants pass away?" remarked a very famous microbiologist to me, soon after the death of Carl Woese in late 2012. I teach microbiology and introductory cell and molecular biology at a small undergraduate institution; Woese's example and contributions have long been part of every class I teach...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.28002
更新日期:2014-01-01 00:00:00
abstract::The non-coding roX1 and roX2 RNAs are components of the MSL dosage compensation complex in Drosophila. We found that multiple species of roX2 RNA are produced by alternative splicing, with one major and at least 20 different minor forms associated with MSL proteins. The alternative forms are generated by variable usag...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.2.4.2473
更新日期:2005-10-01 00:00:00