{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:27:48Z","timestamp":1780504068341,"version":"3.54.1"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T00:00:00Z","timestamp":1522713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Indiana University Grand Challenges Program"},{"name":"The Precision Health Initiative"},{"name":"NSERC Discovery Frontiers Program"},{"DOI":"10.13039\/100008316","name":"Baden-W\u00fcrttemberg-Stiftung","doi-asserted-by":"crossref","award":["BWST NCRNA 008"],"award-info":[{"award-number":["BWST NCRNA 008"]}],"id":[{"id":"10.13039\/100008316","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["BA2168\/11-1 SPP 1738"],"award-info":[{"award-number":["BA2168\/11-1 SPP 1738"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Long non-coding RNAs (lncRNAs) are defined as transcripts longer than 200 nt that do not get translated into proteins. Often these transcripts are processed (spliced, capped and polyadenylated) and some are known to have important biological functions. However, most lncRNAs have unknown or poorly understood functions. Nevertheless, because of their potential role in cancer, lncRNAs are receiving a lot of attention, and the need for computational tools to predict their possible mechanisms of action is more than ever. Fundamentally, most of the known lncRNA mechanisms involve RNA\u2013RNA and\/or RNA\u2013protein interactions. Through accurate predictions of each kind of interaction and integration of these predictions, it is possible to elucidate potential mechanisms for a given lncRNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we introduce MechRNA, a pipeline for corroborating RNA\u2013RNA interaction prediction and protein binding prediction for identifying possible lncRNA mechanisms involving specific targets or on a transcriptome-wide scale. The first stage uses a version of IntaRNA2 with added functionality for efficient prediction of RNA\u2013RNA interactions with very long input sequences, allowing for large-scale analysis of lncRNA interactions with little or no loss of optimality. The second stage integrates protein binding information pre-computed by GraphProt, for both the lncRNA and the target. The final stage involves inferring the most likely mechanism for each lncRNA\/target pair. This is achieved by generating candidate mechanisms from the predicted interactions, the relative locations of these interactions and correlation data, followed by selection of the most likely mechanistic explanation using a combined P-value. We applied MechRNA on a number of recently identified cancer-related lncRNAs (PCAT1, PCAT29 and ARLnc1) and also on two well-studied lncRNAs (PCA3 and 7SL). This led to the identification of hundreds of high confidence potential targets for each lncRNA and corresponding mechanisms. These predictions include the known competitive mechanism of 7SL with HuR for binding on the tumor suppressor TP53, as well as mechanisms expanding what is known about PCAT1 and ARLn1 and their targets BRCA2 and AR, respectively. For PCAT1-BRCA2, the mechanism involves competitive binding with HuR, which we confirmed using HuR immunoprecipitation assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>MechRNA is available for download at https:\/\/bitbucket.org\/compbio\/mechrna.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty208","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T23:12:03Z","timestamp":1522192323000},"page":"3101-3110","source":"Crossref","is-referenced-by-count":64,"title":["MechRNA: prediction of lncRNA mechanisms from RNA\u2013RNA and RNA\u2013protein interactions"],"prefix":"10.1093","volume":"34","author":[{"given":"Alexander R","family":"Gawronski","sequence":"first","affiliation":[{"name":"Computing Science, Simon Fraser University, Burnaby BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Uhl","sequence":"additional","affiliation":[{"name":"Centre for Biological Signalling Studies, University of Freiburg, Freiburg im Breisgau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI, USA"},{"name":"Department of Computational Medicine and Bioinformatics, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4379-1231","authenticated-orcid":false,"given":"Yen-Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Computing Science, Simon Fraser University, Burnaby BC, Canada"},{"name":"Vancouver Prostate Centre, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashar S","family":"Niknafs","sequence":"additional","affiliation":[{"name":"Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varune R","family":"Ramnarine","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Malik","sequence":"additional","affiliation":[{"name":"Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Feng","sequence":"additional","affiliation":[{"name":"Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA"},{"name":"Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arul M","family":"Chinnaiyan","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI, USA"},{"name":"Department of Computational Medicine and Bioinformatics, Ann Arbor, MI, USA"},{"name":"Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA"},{"name":"Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin C","family":"Collins","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S Cenk","family":"Sahinalp","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC, Canada"},{"name":"Department of Computer Science, Indiana University, Bloomington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Backofen","sequence":"additional","affiliation":[{"name":"Centre for Biological Signalling Studies, University of Freiburg, Freiburg im Breisgau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,3]]},"reference":[{"key":"2023012704182479100_bty208-B1","doi-asserted-by":"crossref","first-page":"10099","DOI":"10.1093\/nar\/gku686","article-title":"7SL RNA represses p53 translation by competing with HuR","volume":"42","author":"Abdelmohsen","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023012704182479100_bty208-B2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1089\/cmb.2006.13.267","article-title":"RNA-RNA interaction prediction and antisense RNA target search","volume":"13","author":"Alkan","year":"2006","journal-title":"J. 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