keyword
MENU ▼
Read by QxMD icon Read
search

adrian krainer

keyword
https://www.readbyqxmd.com/read/29449409/a-human-specific-switch-of-alternatively-spliced-afmid-isoforms-contributes-to-tp53-mutations-and-tumor-recurrence-in-hepatocellular-carcinoma
#1
Kuan-Ting Lin, Wai Kit Ma, Juergen Scharner, Yun-Ru Liu, Adrian R Krainer
Pre-mRNA splicing can contribute to the switch of cell identity that occurs in carcinogenesis. Here, we analyze a large collection of RNA-seq data sets and report that splicing changes in hepatocyte-specific enzymes, such as AFMID and KHK , are associated with HCC patients' survival and relapse. The switch of AFMID isoforms is an early event in HCC development and is associated with driver mutations in TP53 and ARID1A The switch of AFMID isoforms is human-specific and not detectable in other species, including primates...
February 15, 2018: Genome Research
https://www.readbyqxmd.com/read/29220503/downregulation-of-survivin-contributes-to-cell-cycle-arrest-during-postnatal-cardiac-development-in-a-severe-spinal-muscular-atrophy-mouse-model
#2
Lei Sheng, Bo Wan, Pengchao Feng, Junjie Sun, Frank Rigo, C Frank Bennett, Martin Akerman, Adrian R Krainer, Yimin Hua
Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, characterized by progressive degeneration of spinal-cord motor neurons, leading to atrophy of skeletal muscles. However, accumulating evidence indicates that it is a multi-system disorder, particularly in its severe forms. Several studies delineated structural and functional cardiac abnormalities in SMA patients and mouse models, yet the abnormalities have been primarily attributed to autonomic dysfunction. Here, we show in a severe mouse model that its cardiomyocytes undergo G0/G1 cell-cycle arrest and enhanced apoptosis during postnatal development...
December 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29133793/binding-to-smn2-pre-mrna-protein-complex-elicits-specificity-for-small-molecule-splicing-modifiers
#3
Manaswini Sivaramakrishnan, Kathleen D McCarthy, Sébastien Campagne, Sylwia Huber, Sonja Meier, Angélique Augustin, Tobias Heckel, Hélène Meistermann, Melanie N Hug, Pascale Birrer, Ahmed Moursy, Sarah Khawaja, Roland Schmucki, Nikos Berntenis, Nicolas Giroud, Sabrina Golling, Manuel Tzouros, Balazs Banfai, Gonzalo Duran-Pacheco, Jens Lamerz, Ying Hsiu Liu, Thomas Luebbers, Hasane Ratni, Martin Ebeling, Antoine Cléry, Sergey Paushkin, Adrian R Krainer, Frédéric H-T Allain, Friedrich Metzger
Small molecule splicing modifiers have been previously described that target the general splicing machinery and thus have low specificity for individual genes. Several potent molecules correcting the splicing deficit of the SMN2 (survival of motor neuron 2) gene have been identified and these molecules are moving towards a potential therapy for spinal muscular atrophy (SMA). Here by using a combination of RNA splicing, transcription, and protein chemistry techniques, we show that these molecules directly bind to two distinct sites of the SMN2 pre-mRNA, thereby stabilizing a yet unidentified ribonucleoprotein (RNP) complex that is critical to the specificity of these small molecules for SMN2 over other genes...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29024433/cation-induced-stabilization-and-denaturation-of-dna-origami-nanostructures-in-urea-and-guanidinium-chloride
#4
Saminathan Ramakrishnan, Georg Krainer, Guido Grundmeier, Michael Schlierf, Adrian Keller
The stability of DNA origami nanostructures under various environmental conditions constitutes an important issue in numerous applications, including drug delivery, molecular sensing, and single-molecule biophysics. Here, the effect of Na(+) and Mg(2+) concentrations on DNA origami stability is investigated in the presence of urea and guanidinium chloride (GdmCl), two strong denaturants commonly employed in protein folding studies. While increasing concentrations of both cations stabilize the DNA origami nanostructures against urea denaturation, they are found to promote DNA origami denaturation by GdmCl...
October 12, 2017: Small
https://www.readbyqxmd.com/read/28598482/correction-structural-stability-of-dna-origami-nanostructures-in-the-presence-of-chaotropic-agents
#5
Saminathan Ramakrishnan, Georg Krainer, Guido Grundmeier, Michael Schlierf, Adrian Keller
Correction for 'Structural stability of DNA origami nanostructures in the presence of chaotropic agents' by Saminathan Ramakrishnan et al., Nanoscale, 2016, 8, 10398-10405.
June 9, 2017: Nanoscale
https://www.readbyqxmd.com/read/28460014/a-44g-transition-in-smn2-intron-6-protects-patients-with-spinal-muscular-atrophy
#6
Xingxing Wu, Shu-Huei Wang, Junjie Sun, Adrian R Krainer, Yimin Hua, Thomas W Prior
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by reduced expression of survival of motor neuron (SMN), a protein expressed in humans by two paralogous genes, SMN1 and SMN2. These genes are nearly identical, except for 10 single-nucleotide differences and a 5-nucleotide insertion in SMN2. SMA is subdivided into four main types, with type I being the most severe. SMN2 copy number is a key positive modifier of the disease, but it is not always inversely correlated with clinical severity. We previously reported the c...
July 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28270613/smn-deficiency-in-severe-models-of-spinal-muscular-atrophy-causes-widespread-intron-retention-and-dna-damage
#7
Mohini Jangi, Christina Fleet, Patrick Cullen, Shipra V Gupta, Shila Mekhoubad, Eric Chiao, Norm Allaire, C Frank Bennett, Frank Rigo, Adrian R Krainer, Jessica A Hurt, John P Carulli, John F Staropoli
Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease, is the leading monogenic cause of infant mortality. Homozygous loss of the gene survival of motor neuron 1 (SMN1) causes the selective degeneration of lower motor neurons and subsequent atrophy of proximal skeletal muscles. The SMN1 protein product, survival of motor neuron (SMN), is ubiquitously expressed and is a key factor in the assembly of the core splicing machinery. The molecular mechanisms by which disruption of the broad functions of SMN leads to neurodegeneration remain unclear...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27662573/a-broad-set-of-chromatin-factors-influences-splicing
#8
Eric Allemand, Michael P Myers, Jose Garcia-Bernardo, Annick Harel-Bellan, Adrian R Krainer, Christian Muchardt
Several studies propose an influence of chromatin on pre-mRNA splicing, but it is still unclear how widespread and how direct this phenomenon is. We find here that when assembled in vivo, the U2 snRNP co-purifies with a subset of chromatin-proteins, including histones and remodeling complexes like SWI/SNF. Yet, an unbiased RNAi screen revealed that the outcome of splicing is influenced by a much larger variety of chromatin factors not all associating with the spliceosome. The availability of this broad range of chromatin factors impacting splicing further unveiled their very context specific effect, resulting in either inclusion or skipping, depending on the exon under scrutiny...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27557711/rna-sequencing-of-a-mouse-model-of-spinal-muscular-atrophy-reveals-tissue-wide-changes-in-splicing-of-u12-dependent-introns
#9
Thomas Koed Doktor, Yimin Hua, Henriette Skovgaard Andersen, Sabrina Brøner, Ying Hsiu Liu, Anna Wieckowska, Maja Dembic, Gitte Hoffmann Bruun, Adrian R Krainer, Brage Storstein Andresen
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder caused by insufficient levels of the Survival of Motor Neuron (SMN) protein. SMN is expressed ubiquitously and functions in RNA processing pathways that include trafficking of mRNA and assembly of snRNP complexes. Importantly, SMA severity is correlated with decreased snRNP assembly activity. In particular, the minor spliceosomal snRNPs are affected, and some U12-dependent introns have been reported to be aberrantly spliced in patient cells and animal models...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27530828/splicing-factor-alterations-in-cancers
#10
REVIEW
Olga Anczuków, Adrian R Krainer
Tumor-associated alterations in RNA splicing result either from mutations in splicing-regulatory elements or changes in components of the splicing machinery. This review summarizes our current understanding of the role of splicing-factor alterations in human cancers. We describe splicing-factor alterations detected in human tumors and the resulting changes in splicing, highlighting cell-type-specific similarities and differences. We review the mechanisms of splicing-factor regulation in normal and cancer cells...
September 2016: RNA
https://www.readbyqxmd.com/read/27380775/global-identification-of-hnrnp-a1-binding-sites-for-sso-based-splicing-modulation
#11
Gitte H Bruun, Thomas K Doktor, Jonas Borch-Jensen, Akio Masuda, Adrian R Krainer, Kinji Ohno, Brage S Andresen
BACKGROUND: Many pathogenic genetic variants have been shown to disrupt mRNA splicing. Besides splice mutations in the well-conserved splice sites, mutations in splicing regulatory elements (SREs) may deregulate splicing and cause disease. A promising therapeutic approach is to compensate for this deregulation by blocking other SREs with splice-switching oligonucleotides (SSOs). However, the location and sequence of most SREs are not well known. RESULTS: Here, we used individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) to establish an in vivo binding map for the key splicing regulatory factor hnRNP A1 and to generate an hnRNP A1 consensus binding motif...
July 5, 2016: BMC Biology
https://www.readbyqxmd.com/read/27142120/structural-stability-of-dna-origami-nanostructures-in-the-presence-of-chaotropic-agents
#12
Saminathan Ramakrishnan, Georg Krainer, Guido Grundmeier, Michael Schlierf, Adrian Keller
DNA origami represent powerful platforms for single-molecule investigations of biomolecular processes. The required structural integrity of the DNA origami may, however, pose significant limitations regarding their applicability, for instance in protein folding studies that require strongly denaturing conditions. Here, we therefore report a detailed study on the stability of 2D DNA origami triangles in the presence of the strong chaotropic denaturing agents urea and guanidinium chloride (GdmCl) and its dependence on concentration and temperature...
May 21, 2016: Nanoscale
https://www.readbyqxmd.com/read/26701265/differentiation-of-mammary-tumors-and-reduction-in-metastasis-upon-malat1-lncrna-loss
#13
Gayatri Arun, Sarah Diermeier, Martin Akerman, Kung-Chi Chang, J Erby Wilkinson, Stephen Hearn, Youngsoo Kim, A Robert MacLeod, Adrian R Krainer, Larry Norton, Edi Brogi, Mikala Egeblad, David L Spector
Genome-wide analyses have identified thousands of long noncoding RNAs (lncRNAs). Malat1 (metastasis-associated lung adenocarcinoma transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genetic loss or systemic knockdown of Malat1 using antisense oligonucleotides (ASOs) in the MMTV (mouse mammary tumor virus)-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by significant differentiation into cystic tumors and a reduction in metastasis...
January 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/26655495/antisense-oligonucleotide-directed-inhibition-of-nonsense-mediated-mrna-decay
#14
Tomoki T Nomakuchi, Frank Rigo, Isabel Aznarez, Adrian R Krainer
Nonsense-mediated mRNA decay (NMD) is a cellular quality-control mechanism that is thought to exacerbate the phenotype of certain pathogenic nonsense mutations by preventing the expression of semi-functional proteins. NMD also limits the efficacy of read-through compound (RTC)-based therapies. Here, we report a gene-specific method of NMD inhibition using antisense oligonucleotides (ASOs) and combine this approach with an RTC to effectively restore the expression of full-length protein from a nonsense-mutant allele...
February 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/26490253/the-spliceosome-a-potential-achilles-heel-of-myc-driven-tumors
#15
Olga Anczuków, Adrian R Krainer
Alterations in RNA splicing are frequent in human tumors. Two recent studies of lymphoma and breast cancer have identified components of the spliceosome - the core splicing machinery - that are essential for malignant transformation driven by the transcription factor MYC. These findings provide a direct link between MYC and RNA splicing deregulation, and raise the exciting possibility of targeting spliceosome components in MYC-driven tumors.
October 22, 2015: Genome Medicine
https://www.readbyqxmd.com/read/26276636/crispr-inversion-of-ctcf-sites-alters-genome-topology-and-enhancer-promoter-function
#16
Ya Guo, Quan Xu, Daniele Canzio, Jia Shou, Jinhuan Li, David U Gorkin, Inkyung Jung, Haiyang Wu, Yanan Zhai, Yuanxiao Tang, Yichao Lu, Yonghu Wu, Zhilian Jia, Wei Li, Michael Q Zhang, Bing Ren, Adrian R Krainer, Tom Maniatis, Qiang Wu
CTCF and the associated cohesin complex play a central role in insulator function and higher-order chromatin organization of mammalian genomes. Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops. To test the functional significance of this observation, we combined CRISPR/Cas9-based genomic-DNA-fragment editing with chromosome-conformation-capture experiments to show that the location and relative orientations of CBSs determine the specificity of long-range chromatin looping in mammalian genomes, using protocadherin (Pcdh) and β-globin as model genes...
August 13, 2015: Cell
https://www.readbyqxmd.com/read/26047612/differential-connectivity-of-splicing-activators-and-repressors-to-the-human-spliceosome
#17
Martin Akerman, Oliver I Fregoso, Shipra Das, Cristian Ruse, Mads A Jensen, Darryl J Pappin, Michael Q Zhang, Adrian R Krainer
BACKGROUND: During spliceosome assembly, protein-protein interactions (PPI) are sequentially formed and disrupted to accommodate the spatial requirements of pre-mRNA substrate recognition and catalysis. Splicing activators and repressors, such as SR proteins and hnRNPs, modulate spliceosome assembly and regulate alternative splicing. However, it remains unclear how they differentially interact with the core spliceosome to perform their functions. RESULTS: Here, we investigate the protein connectivity of SR and hnRNP proteins to the core spliceosome using probabilistic network reconstruction based on the integration of interactome and gene expression data...
2015: Genome Biology
https://www.readbyqxmd.com/read/25780112/splicing-still-so-much-to-learn
#18
Adrian R Krainer
No abstract text is available yet for this article.
April 2015: RNA
https://www.readbyqxmd.com/read/25645699/rescue-of-gene-expression-changes-in-an-induced-mouse-model-of-spinal-muscular-atrophy-by-an-antisense-oligonucleotide-that-promotes-inclusion-of-smn2-exon-7
#19
John F Staropoli, Huo Li, Seung J Chun, Norm Allaire, Patrick Cullen, Alice Thai, Christina M Fleet, Yimin Hua, C Frank Bennett, Adrian R Krainer, Doug Kerr, Alexander McCampbell, Frank Rigo, John P Carulli
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by disruption of the survival motor neuron 1 (SMN1) gene, partly compensated for by the paralogous gene SMN2. Exon 7 inclusion is critical for full-length SMN protein production and occurs at a much lower frequency for SMN2 than for SMN1. Antisense oligonucleotide (ASO)-mediated blockade of an intron 7 splicing silencer was previously shown to promote inclusion of SMN2 exon 7 in SMA mouse models and mediate phenotypic rescue. However, downstream molecular consequences of this ASO therapy have not been defined...
April 2015: Genomics
https://www.readbyqxmd.com/read/25583329/motor-neuron-cell-nonautonomous-rescue-of-spinal-muscular-atrophy-phenotypes-in-mild-and-severe-transgenic-mouse-models
#20
Yimin Hua, Ying Hsiu Liu, Kentaro Sahashi, Frank Rigo, C Frank Bennett, Adrian R Krainer
Survival of motor neuron (SMN) deficiency causes spinal muscular atrophy (SMA), but the pathogenesis mechanisms remain elusive. Restoring SMN in motor neurons only partially rescues SMA in mouse models, although it is thought to be therapeutically essential. Here, we address the relative importance of SMN restoration in the central nervous system (CNS) versus peripheral tissues in mouse models using a therapeutic splice-switching antisense oligonucleotide to restore SMN and a complementary decoy oligonucleotide to neutralize its effects in the CNS...
February 1, 2015: Genes & Development
keyword
keyword
67173
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"