Posts tagged ‘RNA’

Genomics

  1. Li X, Xiong X, Yi C. Epitranscriptome sequencing technologies: decoding RNA modifications. Nat Methods. 2016 Dec 29;14(1):23-31. doi: 10.1038/nmeth.4110. PubMed PMID: 28032622.
  2. Adamson B, Norman TM, Jost M, Cho MY, Nuñez JK, Chen Y, Villalta JE, Gilbert LA, Horlbeck MA, Hein MY, Pak RA, Gray AN, Gross CA, Dixit A, Parnas O, Regev A, Weissman JS. A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. Cell. 2016 Dec 15;167(7):1867-1882.e21. doi: 10.1016/j.cell.2016.11.048. PubMed PMID: 27984733.
  3. Dixit A, Parnas O, Li B, Chen J, Fulco CP, Jerby-Arnon L, Marjanovic ND, Dionne D, Burks T, Raychowdhury R, Adamson B, Norman TM, Lander ES, Weissman JS, Friedman N, Regev A. Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens. Cell. 2016 Dec 15;167(7):1853-1866.e17. doi: 10.1016/j.cell.2016.11.038. PubMed PMID: 27984732; PubMed Central PMCID: PMC5181115.
  4. Jaitin DA, Weiner A, Yofe I, Lara-Astiaso D, Keren-Shaul H, David E, Salame TM, Tanay A, van Oudenaarden A, Amit I. Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq. Cell. 2016 Dec 15;167(7):1883-1896.e15. doi: 10.1016/j.cell.2016.11.039. PubMed PMID: 27984734.

RNA

  1. Rivas E, Clements J, Eddy SR. A statistical test for conserved RNA structure shows lack of evidence for structure in lncRNAs. Nat Methods. 2017 Jan;14(1):45-48. doi: 10.1038/nmeth.4066. PubMed PMID: 27819659.

Cell cycle

  1. Swaffer MP, Jones AW, Flynn HR, Snijders AP, Nurse P. CDK Substrate Phosphorylation and Ordering the Cell Cycle. Cell. 2016 Dec 15;167(7):1750-1761.e16. doi: 10.1016/j.cell.2016.11.034. PubMed PMID: 27984725; PubMed Central PMCID: PMC5161751.

Genome Editing

  1. Pawluk A, Amrani N, Zhang Y, Garcia B, Hidalgo-Reyes Y, Lee J, Edraki A, Shah M, Sontheimer EJ, Maxwell KL, Davidson AR. Naturally Occurring Off-Switches for CRISPR-Cas9. Cell. 2016 Dec 15;167(7):1829-1838.e9. doi: 10.1016/j.cell.2016.11.017. PubMed PMID: 27984730.
  2. Adamson B, Norman TM, Jost M, Cho MY, Nuñez JK, Chen Y, Villalta JE, Gilbert LA, Horlbeck MA, Hein MY, Pak RA, Gray AN, Gross CA, Dixit A, Parnas O, Regev A, Weissman JS. A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. Cell. 2016 Dec 15;167(7):1867-1882.e21. doi: 10.1016/j.cell.2016.11.048. PubMed PMID: 27984733.
  3. Dixit A, Parnas O, Li B, Chen J, Fulco CP, Jerby-Arnon L, Marjanovic ND, Dionne D, Burks T, Raychowdhury R, Adamson B, Norman TM, Lander ES, Weissman JS, Friedman N, Regev A. Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens. Cell. 2016 Dec 15;167(7):1853-1866.e17. doi: 10.1016/j.cell.2016.11.038. PubMed PMID: 27984732; PubMed Central PMCID: PMC5181115.
  4. Jaitin DA, Weiner A, Yofe I, Lara-Astiaso D, Keren-Shaul H, David E, Salame TM, Tanay A, van Oudenaarden A, Amit I. Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq. Cell. 2016 Dec 15;167(7):1883-1896.e15. doi: 10.1016/j.cell.2016.11.039. PubMed PMID: 27984734.
  5. Sheridan C. CRISPR therapeutics push into human testing. Nat Biotechnol. 2017 Jan 10;35(1):3-5. doi: 10.1038/nbt0117-3. PubMed PMID: 28072788.

Zebrafish

  1. Reade A, Motta-Mena LB, Gardner KH, Stainier DY, Weiner OD, Woo S. TAEL: A zebrafish-optimized optogenetic gene expression system with fine spatial and temporal control. Development. 2016 Dec 19. pii: dev.139238. [Epub ahead of print] PubMed PMID: 27993986.

Stem Cells

  1. Mandai M, Fujii M, Hashiguchi T, Sunagawa GA, Ito S, Sun J, Kaneko J, Sho J, Yamada C, Takahashi M. iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice. Stem Cell Reports. 2017 Jan 10;8(1):69-83. doi: 10.1016/j.stemcr.2016.12.008. PubMed PMID: 28076757.

				

A fundamental but elusive step in the early evolution of life on Earth has been replicated in a laboratory.

Researchers synthesized the basic ingredients of RNA, a molecule from which the simplest self-replicating structures are made. Until now, they couldn’t explain how these ingredients might have formed.

….

No matter how they combined the ingredients — a sugar, a phosphate, and one of four different nitrogenous molecules, or nucleobases — ribonucleotides just wouldn’t form. Sutherland’s team took a different approach “and successfully synthesized RNA” in a laboratory conditions resembled those of the life-originating “warm little pond”.

References:

Life’s First Spark Re-Created in the Laboratory [Wired]

Powner MW, Gerland B, Sutherland JD. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature. 2009 May 14;459(7244):239-42. [PubMed][Nature]

We briefly mentioned the idea of silent mutation in the lab meeting the other day when we discussed how DNA mutations can cause diseases. In general, a polymorphism in the wobble (3rd) position of the DNA codon often would not change the amino acid sequence. However, that doesn’t mean everything would be the same or the polymorphism would have no effect on the resulting system. It has long been known that there is codon bias, the preference of using particular codons, among different organisms. This may have implications on the fitness of the animals and evolution.

Josh Plotkin’s group at the University of Pennsylvania has recently done a very interesting study on this topic in Science magazine. They synthesized a synthetic library of 154 green fluorescent protein (GFP) with an average of 114 silent mutations between each pair. They found the expressing of these GFPs in E. Coli, as measured by fluorescence of the GFP, can vary as much as 250 fold! Further analyses revealed that this expression difference did not correlate with the codon bias but more to the secondary structures of the RNA.

As it turned out, RNA with more stable secondary structure was harder to be translated into protein and hence a lower expression level. Also, the stability near 5′ start codon explained most of the expression variation, which indicates the rate limiting step of gene expression was primarily translation initiation. They further predicted and experimentally validated GFP variants with rare codon usage, which presumably were more difficult to produce, would be highly expressed if attached with a 5′ sequence with weaker RNA secondary structure. Therefore silent mutations are not that silent after all, it depends on whether you have the right ear to hear.

Reference

Kudla G, Murray AW, Tollervey D, Plotkin JB. Coding-sequence determinants of gene expression in Escherichia coli. Science. 2009 Apr 10;324(5924):255-8.Click here to read [PubMed][Science]