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However, processed pseudogenes are not able to trigger NMD due to their lack of introns. It is largely unknown whether they have evolved other surveillance mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here, we find that the RNAs of pseudogenes, especially processed pseudogenes, have dramatically higher m\n                      <jats:sup>6<\/jats:sup>\n                      A levels than their cognate protein-coding genes, associated with de novo m\n                      <jats:sup>6<\/jats:sup>\n                      A peaks and motifs in human cells. Furthermore, pseudogenes have rapidly accumulated m\n                      <jats:sup>6<\/jats:sup>\n                      A motifs during evolution. The m\n                      <jats:sup>6<\/jats:sup>\n                      A sites of pseudogenes are evolutionarily younger than neutral sites and their m\n                      <jats:sup>6<\/jats:sup>\n                      A levels are increasing, supporting the idea that m\n                      <jats:sup>6<\/jats:sup>\n                      A on the RNAs of pseudogenes is under positive selection. We then find that the m\n                      <jats:sup>6<\/jats:sup>\n                      A RNA modification of processed, rather than unprocessed, pseudogenes promotes cytosolic RNA degradation and attenuates interference with the RNAs of their cognate protein-coding genes. We experimentally validate the m\n                      <jats:sup>6<\/jats:sup>\n                      A RNA modification of two processed pseudogenes,\n                      <jats:italic>DSTNP2<\/jats:italic>\n                      and\n                      <jats:italic>NAP1L4P1<\/jats:italic>\n                      , which promotes the RNA degradation of both pseudogenes and their cognate protein-coding genes\n                      <jats:italic>DSTN<\/jats:italic>\n                      and\n                      <jats:italic>NAP1L4<\/jats:italic>\n                      . In addition, the m\n                      <jats:sup>6<\/jats:sup>\n                      A of\n                      <jats:italic>DSTNP2<\/jats:italic>\n                      regulation of DSTN is partially dependent on the miRNA miR-362-5p.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our discovery reveals a novel evolutionary role of m\n                      <jats:sup>6<\/jats:sup>\n                      A RNA modification in cleaning up the unnecessary processed pseudogene transcripts to attenuate their interference with the regulatory network of protein-coding genes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13059-021-02402-2","type":"journal-article","created":{"date-parts":[[2021,6,13]],"date-time":"2021-06-13T12:02:21Z","timestamp":1623585741000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes"],"prefix":"10.1186","volume":"22","author":[{"given":"Liqiang","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weisheng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan Ohtan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2577-7575","authenticated-orcid":false,"given":"Jinkai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,13]]},"reference":[{"issue":"2","key":"2402_CR1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/nsmb.1550","volume":"16","author":"S Brogna","year":"2009","unstructured":"Brogna S, Wen J. 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