{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:55:41Z","timestamp":1790877341935,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Cell Biology","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"award":["R35GM133737"],"award-info":[{"award-number":["R35GM133737"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Negative-feedback oscillators require a delay between the accumulation of a repressor\u2019s mRNA and the action of its protein. In the circadian clock, this delay has been attributed largely to post-translational control of PERIOD (PER) stability and nuclear entry. The RNA-binding proteins shown to regulate\n                  <jats:italic>per<\/jats:italic>\n                  translation, ATAXIN-2 and its partners, promote it, leaving open whether any step holds clock transcripts back before they are translated. Here, using time-resolved miniTurbo proximity labeling of endogenous PER across four phases of the circadian cycle in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  clock neurons, we define a 252-protein PER proximitome that partitions into a nuclear arm and a cytoplasmic RNA-metabolism arm. A behavioral RNAi screen identified two P-body components, the DEAD-box helicase Me31B (DDX6) and the 5\u2032\u20133\u2032 exonuclease Pacman (Pcm; XRN1), as strong regulators of circadian rhythms. Using single-molecule RNA-FISH, proximity RNA editing and ribosome profiling, we show that as\n                  <jats:italic>per<\/jats:italic>\n                  and\n                  <jats:italic>tim<\/jats:italic>\n                  transcripts accumulate, they localize to Me31B-labeled P-bodies and are poorly translated, most prominently at ZT12. Me31B knockdown disrupts P-bodies and releases\n                  <jats:italic>per<\/jats:italic>\n                  mRNA from them, causing PER to accumulate earlier and to \u223c2-fold higher levels, whereas Me31B overexpression delays PER accumulation and lengthens the free-running period by \u223c2 h. Knockdown of Pcm, in contrast, impairs clearance of\n                  <jats:italic>per<\/jats:italic>\n                  mRNA, sustaining PER and TIM accumulation, prolonging the repression phase and abolishing cycling of \u223c89% of rhythmic transcripts. Together, these findings identify P-body sequestration as a repressive step that delays repressor synthesis, and Pcm-dependent decay as required to end repression on time. Given the deep conservation of DDX6 and XRN1, RNP compartments may provide a conserved means of generating delay in circadian and other negative-feedback circuits.\n                <\/jats:p>","DOI":"10.64898\/2026.09.28.754909","type":"posted-content","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:50:16Z","timestamp":1790679016000},"source":"Crossref","is-referenced-by-count":0,"title":["P-body sequestration of clock transcripts delays repressor synthesis to set circadian period in\n                  <i>Drosophila<\/i>"],"prefix":"10.64898","author":[{"given":"Yangbo","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-1217","authenticated-orcid":false,"given":"Shrabastee","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5870-341X","authenticated-orcid":false,"given":"Swathi","family":"Yadlapalli","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI"},{"name":"Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100109501722000_2026.09.28.754909v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-387690-4.00005-2"},{"key":"2026100109501722000_2026.09.28.754909v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.150"},{"key":"2026100109501722000_2026.09.28.754909v1.3","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1995.0153"},{"key":"2026100109501722000_2026.09.28.754909v1.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2036281100"},{"key":"2026100109501722000_2026.09.28.754909v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(02)75249-1"},{"key":"2026100109501722000_2026.09.28.754909v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2530"},{"key":"2026100109501722000_2026.09.28.754909v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/343536a0"},{"key":"2026100109501722000_2026.09.28.754909v1.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-08-02749.1990"},{"key":"2026100109501722000_2026.09.28.754909v1.9","doi-asserted-by":"crossref","unstructured":"Xiao, Y. , Yuan, Y. , Jimenez, M. , Soni, N. & Yadlapalli, S . 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