StarScan: a web server for scanning small RNA targets from degradome sequencing data

Endogenous small non-coding RNAs (sRNAs), including microRNAs, PIWI-interacting RNAs and small interfering RNAs, play important gene regulatory roles in animals and plants by pairing to the protein-coding and non-coding transcripts. However, computationally assigning these various sRNAs to their regulatory target genes remains technically challenging. Recently, a high-throughput degradome sequencing method was applied to identify biologically relevant sRNA cleavage sites. In this study, an integrated web-based tool, StarScan (sRNA target Scan), was developed for scanning sRNA targets using degradome sequencing data from 20 species. Given a sRNA sequence from plants or animals, our web server performs an ultrafast and exhaustive search for potential sRNA–target interactions in annotated and unannotated genomic regions. The interactions between small RNAs and target transcripts were further evaluated using a novel tool, alignScore. A novel tool, degradomeBinomTest, was developed to quantify the abundance of degradome fragments located at the 9–11th nucleotide from the sRNA 5′ end. This is the first web server for discovering potential sRNA-mediated RNA cleavage events in plants and animals, which affords mechanistic insights into the regulatory roles of sRNAs. The StarScan web server is available at http://mirlab.sysu.edu.cn/starscan/.

[1]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[2]  G. Calin,et al.  MicroRNAome genome: A treasure for cancer diagnosis and therapy , 2014, CA: a cancer journal for clinicians.

[3]  Toshiaki Watanabe,et al.  Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline , 2015, Genome research.

[4]  Blake C Meyers,et al.  sPARTA: a parallelized pipeline for integrated analysis of plant miRNA and cleaved mRNA data sets, including new miRNA target-identification software , 2014, Nucleic acids research.

[5]  Webb Miller,et al.  CleaveLand: a pipeline for using degradome data to find cleaved small RNA targets , 2009, Bioinform..

[6]  Nicolas Bouché,et al.  A non-canonical plant microRNA target site , 2014, Nucleic Acids Research.

[7]  Weixiong Zhang,et al.  SeqTar: an effective method for identifying microRNA guided cleavage sites from degradome of polyadenylated transcripts in plants , 2011, Nucleic acids research.

[8]  Phillip D Zamore,et al.  Cnidarian microRNAs frequently regulate targets by cleavage , 2014, Genome research.

[9]  Mary Goldman,et al.  The UCSC Genome Browser database: extensions and updates 2011 , 2011, Nucleic Acids Res..

[10]  S. Luo,et al.  Global identification of microRNA–target RNA pairs by parallel analysis of RNA ends , 2008, Nature Biotechnology.

[11]  Pamela J Green,et al.  Construction of Parallel Analysis of RNA Ends (PARE) libraries for the study of cleaved miRNA targets and the RNA degradome , 2009, Nature Protocols.

[12]  M. Kimmel,et al.  Conflict of interest statement. None declared. , 2010 .

[13]  Edwards Allen,et al.  P1/HC-Pro, a viral suppressor of RNA silencing, interferes with Arabidopsis development and miRNA unction. , 2003, Developmental cell.

[14]  Toshiaki Watanabe,et al.  Posttranscriptional regulation of gene expression by Piwi proteins and piRNAs. , 2014, Molecular cell.

[15]  M. A. Rector,et al.  Endogenous and Silencing-Associated Small RNAs in Plants Online version contains Web-only data. Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.003210. , 2002, The Plant Cell Online.

[16]  Shunmin He,et al.  MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes , 2015, Cell Research.

[17]  Yves Van de Peer,et al.  TAPIR, a web server for the prediction of plant microRNA targets, including target mimics , 2010, Bioinform..

[18]  D. Bartel,et al.  Endogenous siRNA and miRNA Targets Identified by Sequencing of the Arabidopsis Degradome , 2008, Current Biology.

[19]  Cole Trapnell,et al.  Ultrafast and memory-efficient alignment of short DNA sequences to the human genome , 2009, Genome Biology.

[20]  J. Carrington,et al.  miRNA Target Prediction in Plants. , 2010, Methods in molecular biology.

[21]  Sean R. Davis,et al.  NCBI GEO: archive for functional genomics data sets—update , 2012, Nucleic Acids Res..

[22]  Bronwen L. Aken,et al.  GENCODE: The reference human genome annotation for The ENCODE Project , 2012, Genome research.

[23]  C. Norbury,et al.  The Long and Short of MicroRNA , 2013, Cell.

[24]  Kyle Kai-How Farh,et al.  Expanding the microRNA targeting code: functional sites with centered pairing. , 2010, Molecular cell.

[25]  Gregory J. Hannon,et al.  Diverse endonucleolytic cleavage sites in the mammalian transcriptome depend upon microRNAs, Drosha, and additional nucleases. , 2010, Molecular cell.

[26]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

[27]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[28]  Mary Goldman,et al.  The UCSC Genome Browser database: extensions and updates 2013 , 2012, Nucleic Acids Res..

[29]  R. Lister,et al.  A link between RNA metabolism and silencing affecting Arabidopsis development. , 2008, Developmental cell.

[30]  Jørgen Kjems,et al.  miRNA‐dependent gene silencing involving Ago2‐mediated cleavage of a circular antisense RNA , 2011, The EMBO journal.

[31]  Phillip D Zamore,et al.  The RNA-Induced Silencing Complex Is a Mg2+-Dependent Endonuclease , 2004, Current Biology.

[32]  Andrew M. Jenkinson,et al.  Ensembl 2009 , 2008, Nucleic Acids Res..

[33]  Eric C. Lai,et al.  Endogenous small interfering RNAs in animals , 2008, Nature Reviews Molecular Cell Biology.

[34]  Matthew B. Stocks,et al.  PAREsnip: a tool for rapid genome-wide discovery of small RNA/target interactions evidenced through degradome sequencing , 2012, Nucleic acids research.

[35]  Z. Cheng,et al.  Identification of miRNAs and Their Target Genes in Peach (Prunus persica L.) Using High-Throughput Sequencing and Degradome Analysis , 2013, PloS one.

[36]  Hui Zhou,et al.  starBase: a database for exploring microRNA–mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data , 2010, Nucleic Acids Res..

[37]  D. Bartel MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[38]  H. van de Geest,et al.  Identification of microRNA targets in tomato fruit development using high-throughput sequencing and degradome analysis , 2013, Journal of experimental botany.

[39]  Hsien-Da Huang,et al.  miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions , 2013, Nucleic Acids Res..