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N(6)-methyladenosine (m6A) is the most abundant modified base in eukaryotic mRNA and has been linked to diverse effects on mRNA fate. Current mapping approaches localize m6A residues to transcript regions 100-200 nt long but cannot identify precise m6A positions on a transcriptome-wide level. Here we developed m6A individual-nucleotide-resolution(More)
Differentiation of neural stem cells (NSCs) to neurons requires the activation of genes controlled by the repressor element 1 (RE1) silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) protein complex. Important components of REST/NRSF are phosphatases (termed RNA polymerase II C-terminal domain small phosphatases [CTDSPs]) that(More)
Low molecular weight chaperones inhibit protein aggregation and facilitate refolding of partially denatured polypeptides in cells subjected to physical and chemical stresses. The nematode Caenorhabditis elegans provides a system amenable for investigations on roles for chaperone proteins in normal homeostasis and development. We characterized a C. elegans(More)
Implicating particular genes in the generation of complex brain and behavior phenotypes requires multiple lines of evidence. The rarity of most high-impact genetic variants typically precludes the possibility of accruing statistical evidence that they are associated with a given trait. We found that the enrichment of a rare chromosome 22q11.22 deletion in a(More)
Retinitis pigmentosa (RP) is a common hereditary eye disease that causes blindness due to a progressive loss of photoreceptors in the retina. RP can be elicited by mutations that affect the tri-snRNP subunit of the pre-mRNA splicing machinery, but how defects in this essential macromolecular complex transform into a photoreceptor-specific phenotype is(More)
Internal bases in mRNA can be subjected to modifications that influence the fate of mRNA in cells. One of the most prevalent modified bases is found at the 5' end of mRNA, at the first encoded nucleotide adjacent to the 7-methylguanosine cap. Here we show that this nucleotide, N6,2'-O-dimethyladenosine (m6Am), is a reversible modification that influences(More)
PURPOSE In experimental eye research, zebrafish has become a powerful model for human retina disorders. The purpose of the present study is the characterization of antibodies commonly employed in zebrafish models for rod photoreceptor degeneration. METHODS The 1D4 monoclonal antibody, developed against bovine rhodopsin, has been widely used in studies(More)
Tudor domains are widespread among proteins involved in RNA metabolism, but only in a few cases their cellular function has been analyzed in detail. Here, we report on the characterization of the ubiquitously expressed Tudor domain containing protein Tdrd3. Apart from its Tudor domain, we show that Tdrd3 possesses an oligosaccharide/nucleotide binding fold(More)
Pre-mRNA splicing by the spliceosome is an essential step in the maturation of nearly all human mRNAs. Mutations in six spliceosomal proteins, PRPF3, PRPF4, PRPF6, PRPF8, PRPF31 and SNRNP200, cause retinitis pigmentosa (RP), a disease characterized by progressive photoreceptor degeneration. All splicing factors linked to RP are constituents of the U4/U6.U5(More)