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New Species Discovered, Thanks to Flickr. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Sciencemagazine: High-res crystal structure... Science Magazine: Sign In. Specific RNA recognition is usually achieved by specific RNA sequences and/or structures. However, we show here a mechanism by which RNA polymerase II (Pol II) transcripts are classified according to their length. The heterotetramer of the heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2 measures the length of the transcripts like a molecular More Specific RNA recognition is usually achieved by specific RNA sequences and/or structures. However, we show here a mechanism by which RNA polymerase II (Pol II) transcripts are classified according to their length. The heterotetramer of the heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2 measures the length of the transcripts like a molecular ruler, by selectively binding to the unstructured RNA regions longer than 200 to 300 nucleotides.

Science Magazine: Sign In. Science Magazine: Sign In. Ribosome Profiling Shows That miR-430 Reduces Translation Before Causing mRNA Decay in Zebrafish. Comment on “Widespread RNA and DNA Sequence Differences in the Human Transcriptome” Abstract Li et al. (Research Articles, 1 July 2011, p. 53; published online 19 May 2011) reported large numbers of differences between DNA and messenger RNA in human cells, indicating unprecedented levels of RNA editing, and including sequence changes not produced by any of the known RNA editing mechanisms.

However, common sources of systematic errors in high-throughput sequencing technology, which were not properly accounted for in this study, explain most of the claimed differences. Li et al. (1) reported widespread RNA and DNA sequence differences (RDDs) in the human transcriptome, representing all 12 possible residue changes, and suggesting unexpectedly high frequencies and spectra of RNA editing. Because RNA editing and transcriptional noise are known phenomena (2–4), the novelty of this work resides in the extreme extent to which the differences are reported to happen in human cells. Fig. 1 Table 1 A common alignment error occurs when reads span splice junctions. Science Magazine: Sign In. Response to Comments on “Widespread RNA and DNA Sequence Differences in the Human Transcriptome” + Author Affiliations ↵†To whom correspondence should be addressed.

E-mail: vcheung@mail.med.upenn.edu ↵* These authors contributed equally to this work. Abstract Kleinman and Majewski, Pickrell et al., and Lin et al. suggest that mapping and sequencing errors and genetic variants led to false discovery of RNA-DNA sequence differences in our paper. We repeated our analysis using two different sequence alignment methods and carried out additional experiments including whole genome DNA sequencing. The results are consistent with our finding of widespread RNA-DNA sequence differences. We reported uncovering RNA sequences that differ from the underlying DNA sequences (1). Since our publication, several groups (2–5) have published about finding RNA-DNA differences beyond the A-to-G and C-to-U types.

Table 1 Studies that identify RNA-DNA differences. First, we analyzed the sequence data on the 27 individuals using a different alignment program, GSNAP (11). Fig. 1 Fig. 2 Fig. 3 Table 2 Table 3 Fig. 4. Comment on “Widespread RNA and DNA Sequence Differences in the Human Transcriptome” Science Magazine: Sign In. Science Magazine: Sign In. Comment on “Widespread RNA and DNA Sequence Differences in the Human Transcriptome” + Author Affiliations ↵†To whom correspondence should be addressed. E-mail: jin.billy.li@stanford.edu ↵* These authors contributed equally to this work. Abstract Li et al. (Research Articles, 1 July 2011, p. 53; published online 19 May 2011) reported widespread differences between the RNA and DNA sequences of the same human cells, including all 12 possible mismatch types. Before accepting such a fundamental claim, a deeper analysis of the sequencing data is required to discern true differences between RNA and DNA from potential artifacts. By comparing RNA and DNA sequences generated by high-throughput sequencing of human B cells, Li et al. (1) reported finding 10,210 RNA-DNA differences (RDDs) of all 12 possible mismatch categories.

Accurately mapping the short high-throughput sequencing reads is critical for calling RDDs to ensure that RNA- and DNA-derived sequences originate from the same genomic locus. Fig. 1 Percentage of RDDs in duplicated regions. Fig. 2. Science - Video Portal. Science Magazine: Sign In. Genetically encoded sensors are powerful tools for imaging intracellular metabolites and signaling molecules. However, developing sensors is challenging because they require proteins that undergo conformational changes upon binding the desired target molecule. We describe an approach for generating fluorescent sensors based on Spinach, an RNA sequence that binds and activates More Genetically encoded sensors are powerful tools for imaging intracellular metabolites and signaling molecules. However, developing sensors is challenging because they require proteins that undergo conformational changes upon binding the desired target molecule.

We describe an approach for generating fluorescent sensors based on Spinach, an RNA sequence that binds and activates the fluorescence of a small-molecule fluorophore. We show that these sensors can detect a variety of different small molecules in vitro and in living cells. New year, new science. Extinct Genome From Fossil Finger Posted Online. Researchers in Germany today posted the first high-resolution version of an extinct human's genome on the Web site for the Max Planck Institute for Evolutionary Anthropology.

The goal: to allow colleagues to download the most complete sequence data available for free. A year ago, researchers published the first rough draft of the genome of an archaic girl who lived in Denisova Cave, Siberia, at least 30,000 years ago. In January, Max Planck paleogeneticist Svante Pääbo was at a meeting in Sweden when he realized that researchers in other labs were poring over year-old sequence data that was far less complete than what his colleagues had obtained in the lab in the past year using sensitive, new methods to sequence ancient DNA. "I felt bad knowing that we had this very much better version of the same genome and that it would be a few months before it became available," says Pääbo.

A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes. Loss of Function Variants - MacArthur Lab. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. The RNA polymerase II (RNAP II) largest subunit contains a C-terminal domain (CTD) with up to 52 Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 consensus repeats. Serines 2, 5, and 7 are known to be phosphorylated, and these modifications help to orchestrate the interplay between transcription and processing of messenger RNA (mRNA) precursors. Here, we provide More The RNA polymerase II (RNAP II) largest subunit contains a C-terminal domain (CTD) with up to 52 Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 consensus repeats. Serines 2, 5, and 7 are known to be phosphorylated, and these modifications help to orchestrate the interplay between transcription and processing of messenger RNA (mRNA) precursors.

Science Magazine: Sign In. Science Magazine: Sign In. The CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase] adds CCA to the 3′ ends of transfer RNAs (tRNAs), a critical step in tRNA biogenesis that generates the amino acid attachment site. We found that the CCA-adding enzyme plays a key role in tRNA quality control by selectively marking structurally unstable tRNAs and tRNA-like More The CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase] adds CCA to the 3′ ends of transfer RNAs (tRNAs), a critical step in tRNA biogenesis that generates the amino acid attachment site.

We found that the CCA-adding enzyme plays a key role in tRNA quality control by selectively marking structurally unstable tRNAs and tRNA-like small RNAs for degradation. Instead of adding CCA to the 3′ ends of these transcripts, CCA-adding enzymes from all three kingdoms of life add CCACCA. In addition, hypomodified mature tRNAs are subjected to CCACCA addition as part of a rapid tRNA decay pathway in vivo.

Science Magazine: Sign In. Science Magazine: Sign In. Nonhexameric helicases use adenosine triphosphate (ATP) to unzip base pairs in double-stranded nucleic acids (dsNAs). Studies have suggested that these helicases unzip dsNAs in single–base pair increments, consuming one ATP molecule per base pair, but direct evidence for this mechanism is lacking. We used optical tweezers to follow the unwinding More Nonhexameric helicases use adenosine triphosphate (ATP) to unzip base pairs in double-stranded nucleic acids (dsNAs).

Studies have suggested that these helicases unzip dsNAs in single–base pair increments, consuming one ATP molecule per base pair, but direct evidence for this mechanism is lacking. Science Magazine: Sign In. 'Super-Earth' Found in Habitable Zone. JACKSON LAKE, WYOMING—The Milky Way abounds with low-mass planets, including small, rocky ones such as Earth. That's the main conclusion of a team of European astronomers, based on their latest haul of extrasolar planets. The new discoveries—55 new planets, including 19 "super-Earths"—were presented here today at the Extreme Solar Systems II conference by team leader Michel Mayor of the University of Geneva in Switzerland. "We find that 40% of all Sun-like stars are accompanied by at least one planet smaller than Saturn," he says.

The number of Earth-like planets is expected to be even higher. The new planets were found with HARPS (High Accuracy Radial velocity Planet Searcher), an extremely sensitive instrument used to analyze starlight, mounted on the 3.6-meter telescope of the European Southern Observatory (ESO) at Cerro La Silla in northern Chile. HARPS detects the minute periodic wobbles of stars, caused by the gravity of orbiting planets. RNA Mimics of Green Fluorescent Protein. Science Magazine: Sign In. Science Magazine: Sign In. The rules of nucleic acid base-pairing have been used to construct nanoscale architectures and organize biomolecules, but little has been done to apply this technology in vivo. We designed and assembled multidimensional RNA structures and used them as scaffolds for the spatial organization of bacterial metabolism. Engineered RNA modules were More The rules of nucleic acid base-pairing have been used to construct nanoscale architectures and organize biomolecules, but little has been done to apply this technology in vivo.

We designed and assembled multidimensional RNA structures and used them as scaffolds for the spatial organization of bacterial metabolism. Engineered RNA modules were assembled into discrete, one-dimensional, and two-dimensional scaffolds with distinct protein-docking sites and used to control the spatial organization of a hydrogen-producing pathway. Science Magazine: Sign In. Webinar Registration. Science/AAAS | Background - The Neandertal Genome. Science Magazine: Sign In. Science Magazine: Sign In. The ribonuclease (RNase) H class of enzymes degrades the RNA component of RNA:DNA hybrids and is important in nucleic acid metabolism.

RNase H2 is specialized to remove single ribonucleotides [ribonucleoside monophosphates (rNMPs)] from duplex DNA, and its absence in budding yeast has been associated with the accumulation of deletions within More The ribonuclease (RNase) H class of enzymes degrades the RNA component of RNA:DNA hybrids and is important in nucleic acid metabolism. RNase H2 is specialized to remove single ribonucleotides [ribonucleoside monophosphates (rNMPs)] from duplex DNA, and its absence in budding yeast has been associated with the accumulation of deletions within short tandem repeats. Here, we demonstrate that rNMP-associated deletion formation requires the activity of Top1, a topoisomerase that relaxes supercoils by reversibly nicking duplex DNA. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In.