CRISPRlnc: a manually curated database of validated sgRNAs for lncRNAs

Abstract The CRISPR/Cas9 system, as a revolutionary genome editing tool for all areas of molecular biology, provides new opportunities for research on lncRNA’s function. However, designing a CRISPR/Cas9 single guide RNA (sgRNA) for lncRNA is not easy with an unwarrantable effectiveness. Thus, it is worthy of collecting validated sgRNAs, to assist in efficiently choosing sgRNA with an expected activity. CRISPRlnc (http://www.crisprlnc.org or http://crisprlnc.xtbg.ac.cn) is a manually curated database of validated CRISPR/Cas9 sgRNAs for lncRNAs from all species. After manually reviewing more than 200 published literature, the current version of CRISPRlnc contains 305 lncRNAs and 2102 validated sgRNAs across eight species, including mammalian, insect and plant. We handled the ID, position in the genome, sequence and functional description of these lncRNAs, as well as the sequence, protoacceptor-motif (PAM), CRISPR type and validity of their paired sgRNAs. In CRISPRlnc, we provided the tools for browsing, searching and downloading data, as well as online BLAST service and genome browse server. As the first database against the validated sgRNAs of lncRNAs, CRISPRlnc will provide a new and powerful platform to promote CRISPR/Cas9 applications for future functional studies of lncRNAs.

[1]  Tyra G. Wolfsberg,et al.  CRISPRz: a database of zebrafish validated sgRNAs , 2015, Nucleic Acids Res..

[2]  Ji-Long Liu,et al.  Effective knockdown of Drosophila long non-coding RNAs by CRISPR interference , 2016, Nucleic acids research.

[3]  Zhongzheng Cao,et al.  Genome-scale deletion screening of human long non-coding RNAs using a paired-guide RNA CRISPR–Cas9 library , 2016, Nature Biotechnology.

[4]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[5]  Tim J. P. Hubbard,et al.  Dalliance: interactive genome viewing on the web , 2011, Bioinform..

[6]  Luke A. Gilbert,et al.  CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes , 2013, Cell.

[7]  F. Slack,et al.  Junk DNA and the long non-coding RNA twist in cancer genetics , 2015, Oncogene.

[8]  David R. Liu,et al.  Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage , 2016, Nature.

[9]  B. Schroen,et al.  Long noncoding RNAs in cardiac development and ageing , 2015, Nature Reviews Cardiology.

[10]  Evan Bolton,et al.  Database resources of the National Center for Biotechnology Information , 2017, Nucleic Acids Res..

[11]  Ksenia Myacheva,et al.  Challenges of CRISPR/Cas9 applications for long non-coding RNA genes , 2016, Nucleic acids research.

[12]  Steven R. Head,et al.  An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment. , 2014, Molecular cell.

[13]  Alexandro E. Trevino,et al.  Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex , 2014, Nature.

[14]  Howard Y. Chang,et al.  Molecular mechanisms of long noncoding RNAs. , 2011, Molecular cell.

[15]  S. Dhanasekaran,et al.  The landscape of long noncoding RNAs in the human transcriptome , 2015, Nature Genetics.

[16]  G. Condorelli,et al.  Epigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure , 2015, Nature Reviews Cardiology.

[17]  Michael Q. Zhang,et al.  NONCODEV5: a comprehensive annotation database for long non-coding RNAs , 2017, Nucleic Acids Res..

[18]  Luke A. Gilbert,et al.  Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression , 2013, Cell.

[19]  Marcel E. Dinger,et al.  lncRNAdb v2.0: expanding the reference database for functional long noncoding RNAs , 2014, Nucleic Acids Res..

[20]  Maite Huarte.  The emerging role of lncRNAs in cancer , 2015, Nature Medicine.

[21]  Manolis Kellis,et al.  The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. , 2013, Developmental cell.

[22]  Le Cong,et al.  Multiplex Genome Engineering Using CRISPR/Cas Systems , 2013, Science.

[23]  Michael Morse,et al.  Multiple knockout mouse models reveal lincRNAs are required for life and brain development , 2013, eLife.

[24]  A. Fatica,et al.  Long non-coding RNAs: new players in cell differentiation and development , 2013, Nature Reviews Genetics.

[25]  D. Bartel,et al.  Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution , 2011, Cell.

[26]  Howard Y. Chang,et al.  NONCODING RNA: CRISPRi‐based genome‐scale identification of functional long noncoding RNA loci in human cells , 2017 .

[27]  D. Bartel,et al.  lincRNAs: Genomics, Evolution, and Mechanisms , 2013, Cell.

[28]  V. Scaria,et al.  Dynamic Expression of Long Non-Coding RNAs (lncRNAs) in Adult Zebrafish , 2013, PloS one.

[29]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology Information: update , 2004, Nucleic acids research.

[30]  James E. DiCarlo,et al.  RNA-Guided Human Genome Engineering via Cas9 , 2013, Science.

[31]  Michael F. Lin,et al.  Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis. , 2012, Genome research.

[32]  Fangting Wu,et al.  Targeting non-coding RNAs with the CRISPR/Cas9 system in human cell lines , 2014, Nucleic acids research.

[33]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[34]  Jesse M. Engreitz,et al.  Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood , 2017, Nature.

[35]  G. Church,et al.  CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering , 2013, Nature Biotechnology.