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Widespread RNA editing dysregulation in brains from autistic individuals.

Nature neuroscience · 2019 · 22(1): 25-36

Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns …

PMID 30559470 DOI ↗

Patch-Seq Protocol to Analyze the Electrophysiology, Morphology and Transcriptome of Whole Single Neurons Derived From Human Pluripotent Stem Cells.

Frontiers in molecular neuroscience · 2018 · 11: 261

The human brain is composed of a complex assembly of about 171 billion heterogeneous cellular units (86 billion neurons and 85 billion non-neuronal glia cells). A comprehensive description of brain cells is necessary to understand the nervous system in health …

PMID 30147644 DOI ↗

An important class of intron retention events in human erythroblasts is regulated by cryptic exons proposed to function as splicing decoys.

RNA (New York, N.Y.) · 2018 · 24(9): 1255-1265

During terminal erythropoiesis, the splicing machinery in differentiating erythroblasts executes a robust intron retention (IR) program that impacts expression of hundreds of genes. We studied IR mechanisms in the <i>SF3B1</i> splicing factor gene, which expresses ∼50% of its transcripts in …

PMID 29959282 DOI ↗

Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.

Acta neuropathologica · 2018 · 136(3): 405-423

Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched …

PMID 29881994 DOI ↗

Systematic Discovery of RNA Binding Proteins that Regulate MicroRNA Levels.

Molecular cell · 2018 · 69(6): 1005-1016.e7

RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced …

PMID 29547715 DOI ↗

Short poly(A) tails are a conserved feature of highly expressed genes.

Nature structural & molecular biology · 2017 · 24(12): 1057-1063

Poly(A) tails are important elements in mRNA translation and stability, although recent genome-wide studies have concluded that poly(A) tail length is generally not associated with translational efficiency in nonembryonic cells. To investigate whether poly(A) tail size might be coupled to …

PMID 29106412 DOI ↗

Nol12 is a multifunctional RNA binding protein at the nexus of RNA and DNA metabolism.

Nucleic acids research · 2017 · 45(21): 12509-12528

To counteract the breakdown of genome integrity, eukaryotic cells have developed a network of surveillance pathways to prevent and resolve DNA damage. Recent data has recognized the importance of RNA binding proteins (RBPs) in DNA damage repair (DDR) pathways. Here, …

PMID 29069457 DOI ↗

Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer.

Cancer discovery · 2017 · 7(4): 410-423

Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal …

PMID 28188128 DOI ↗

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Stem cell reports · 2017 · 8(4): 1086-1100

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 …

PMID 28410642 DOI ↗

Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing.

Nature genetics · 2017 · 49(3): 457-464

Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg²⁺-dependent 3'-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) …

PMID 28092684 DOI ↗

Tethered Function Assays as Tools to Elucidate the Molecular Roles of RNA-Binding Proteins.

Advances in experimental medicine and biology · 2016 · 907: 61-88

Dynamic regulation of RNA molecules is critical to the survival and development of cells. Messenger RNAs are transcribed in the nucleus as intron-containing pre-mRNAs and bound by RNA-binding proteins, which control their fate by regulating RNA stability, splicing, polyadenylation, translation, …

PMID 27256382 DOI ↗

Experimental and Computational Considerations in the Study of RNA-Binding Protein-RNA Interactions.

Advances in experimental medicine and biology · 2016 · 907: 1-28

After an RNA is transcribed, it undergoes a variety of processing steps that can change the encoded protein sequence (through alternative splicing and RNA editing), regulate the stability of the RNA, and control subcellular localization, timing, and rate of translation. …

PMID 27256380 DOI ↗

Making the cut in the dark genome.

Science (New York, N.Y.) · 2016 · 354(6313): 705-706

PMID 27846591 DOI ↗

Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model.

Genome medicine · 2016 · 8(1): 94

Tuberous sclerosis complex (TSC) is a genetic disease characterized by benign tumor growths in multiple organs and neurological symptoms induced by mTOR hyperfunction. Because the molecular pathology is highly complex and the etiology poorly understood, we employed a defined human …

PMID 27655340 DOI ↗

Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts.

Scientific reports · 2016 · 6: 30896

Hypoplastic left heart syndrome (HLHS) is a fatal congenital heart disease in which the left side of the heart is underdeveloped, impairing the systemic circulation. Underdeveloped left ventricle exerts biomechanical stress on the right ventricle that can progress into heart …

PMID 27485310 DOI ↗

Programmable RNA Tracking in Live Cells with CRISPR/Cas9.

Cell · 2016 · 165(2): 488-96

RNA-programmed genome editing using CRISPR/Cas9 from Streptococcus pyogenes has enabled rapid and accessible alteration of specific genomic loci in many organisms. A flexible means to target RNA would allow alteration and imaging of endogenous RNA transcripts analogous to CRISPR/Cas-based genomic …

PMID 26997482 DOI ↗

Applications of Cas9 as an RNA-programmed RNA-binding protein.

BioEssays : news and reviews in molecular, cellular and developmental biology · 2015 · 37(7): 732-9

The Streptococcus pyogenes CRISPR-Cas system has gained widespread application as a genome editing and gene regulation tool as simultaneous cellular delivery of the Cas9 protein and guide RNAs enables recognition of specific DNA sequences. The recent discovery that Cas9 can …

PMID 25880497 DOI ↗

Nxf1 natural variant E610G is a semi-dominant suppressor of IAP-induced RNA processing defects.

PLoS genetics · 2015 · 11(4): e1005123

Endogenous retroviruses and retrotransposons contribute functional genetic variation in animal genomes. In mice, Intracisternal A Particles (IAPs) are a frequent source of both new mutations and polymorphism across laboratory strains. Intronic IAPs can induce alternative RNA processing choices, including alternative …

PMID 25835743 DOI ↗

RNA-binding proteins in neurodegeneration: Seq and you shall receive.

Trends in neurosciences · 2015 · 38(4): 226-36

As critical players in gene regulation, RNA binding proteins (RBPs) are taking center stage in our understanding of cellular function and disease. In our era of bench-top sequencers and unprecedented computational power, biological questions can be addressed in a systematic, …

PMID 25765321 DOI ↗

A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.

PloS one · 2014 · 9(12): e113258

The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe …

PMID 25474699 DOI ↗

The Period protein homolog LIN-42 negatively regulates microRNA biogenesis in C. elegans.

Developmental biology · 2014 · 390(2): 126-35

MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate gene expression in many multicellular organisms. They are encoded in the genome and transcribed into primary (pri-) miRNAs before two processing steps that ultimately produce the mature miRNA. In order to generate …

PMID 24699545 DOI ↗

Human cytomegalovirus infection of human embryonic stem cell-derived primitive neural stem cells is restricted at several steps but leads to the persistence of viral DNA.

Journal of virology · 2014 · 88(8): 4021-39

Congenital human cytomegalovirus (HCMV) infection is a major cause of central nervous system structural anomalies and sensory impairments. It is likely that the stage of fetal development, as well as the state of differentiation of susceptible cells at the time …

PMID 24453373 DOI ↗

Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans.

PLoS genetics · 2013 · 9(3): e1003353

The let-7 microRNA (miRNA) regulates cellular differentiation across many animal species. Loss of let-7 activity causes abnormal development in Caenorhabditis elegans and unchecked cellular proliferation in human cells, which contributes to tumorigenesis. These defects are due to improper expression of …

PMID 23516374 DOI ↗

Reactivation of fetal splicing programs in diabetic hearts is mediated by protein kinase C signaling.

The Journal of biological chemistry · 2013 · 288(49): 35372-86

Diabetic cardiomyopathy is one of the complications of diabetes that eventually leads to heart failure and death. Aberrant activation of PKC signaling contributes to diabetic cardiomyopathy by mechanisms that are poorly understood. Previous reports indicate that PKC is implicated in …

PMID 24151077 DOI ↗

Differential L1 regulation in pluripotent stem cells of humans and apes.

Nature · 2013 · 503(7477): 525-529

Identifying cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic understanding of the evolution and diversity of our own species. Until now, preserved tissues have been the main source for most comparative studies between …

PMID 24153179 DOI ↗