{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T20:48:01Z","timestamp":1794343681001,"version":"4.9.0"},"reference-count":88,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SPP2453, KR 3593\/6-1"],"award-info":[{"award-number":["SPP2453, KR 3593\/6-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The Signal Recognition Particle (SRP) targets nascent proteins to the Sec61 translocon for import into the endoplasmic reticulum (ER). However, its range of substrates, point of engagement during targeting, and hence full biological impact remain unclear. Here, we examined SRP interactions with the nascent proteome of\n                    <jats:italic>S. cerevisiae<\/jats:italic>\n                    during translation and membrane targeting. SRP binds effectively to transmembrane domains (TMDs) as they emerge from the ribosomal tunnel, but only to a minority of cleavable signal peptides. We identify nascent chain features that promote SRP binding, allowing to develop a predictive algorithm. We show SRP performs a role in triaging nascent ER proteins into distinct targeting routes and downstream maturation processes. Furthermore, ribosomes frequently dissociate from the membrane before completing translocation, allowing the chaperone Ssb to assist folding of emerging cytosolic domains. Ribosomes translating multipass membrane proteins are retargeted to the translocon through repeated SRP interactions with internal TMDs, emphasizing collaboration between SRP and chaperones in membrane protein biogenesis.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-74404-2","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:14:52Z","timestamp":1781622892000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SRP orchestrates protein biogenesis beyond initial ER membrane targeting"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9028-979X","authenticated-orcid":false,"given":"Ilg\u0131n Eser","family":"Kotan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Sartori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudra","family":"Bose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0521-7199","authenticated-orcid":false,"given":"Bernd","family":"Bukau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7552-8393","authenticated-orcid":false,"given":"G\u00fcnter","family":"Kramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"74404_CR1","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1146\/annurev-biochem-072711-164732","volume":"82","author":"D Akopian","year":"2013","unstructured":"Akopian, D., Shen, K., Zhang, X. & Shan, S. -o Signal recognition particle: an essential protein-targeting machine. Annu. Rev. Biochem. 82, 693\u2013721 (2013).","journal-title":"Annu. Rev. Biochem."},{"key":"74404_CR2","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1083\/jcb.91.2.551","volume":"91","author":"P Walter","year":"1981","unstructured":"Walter, P. & Blobel, G. Translocation of proteins across the endoplasmic reticulum. II. Signal recognition protein (SRP) mediates the selective binding to microsomal membranes of in-vitro-assembled polysomes synthesizing secretory protein. J. Cell Biol. 91, 551\u2013556 (1981).","journal-title":"J. Cell Biol."},{"key":"74404_CR3","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1083\/jcb.91.2.557","volume":"91","author":"P Walter","year":"1981","unstructured":"Walter, P. & Blobel, G. Translocation of proteins across the endoplasmic reticulum III. Signal recognition protein (SRP) causes signal sequence-dependent and site-specific arrest of chain elongation that is released by microsomal membranes. J. Cell Biol. 91, 557\u2013561 (1981).","journal-title":"J. Cell Biol."},{"key":"74404_CR4","doi-asserted-by":"publisher","first-page":"4164","DOI":"10.1093\/emboj\/19.15.4164","volume":"19","author":"N Mason","year":"2000","unstructured":"Mason, N., Ciufo, L. F. & Brown, J. D. Elongation arrest is a physiologically important function of signal recognition particle. EMBO J. 19, 4164\u20134174 (2000).","journal-title":"EMBO J."},{"key":"74404_CR5","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.cell.2008.02.049","volume":"133","author":"AKK Lakkaraju","year":"2008","unstructured":"Lakkaraju, A. K. K., Mary, C., Scherrer, A., Johnson, A. E. & Strub, K. SRP keeps polypeptides translocation-competent by slowing translation to match limiting ER-targeting sites. Cell 133, 440\u2013451 (2008).","journal-title":"Cell"},{"key":"74404_CR6","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1083\/jcb.91.2.545","volume":"91","author":"P Walter","year":"1981","unstructured":"Walter, P., Ibrahimi, I. & Blobel, G. Translocation of proteins across the endoplasmic reticulum. I. Signal recognition protein (SRP) binds to in-vitro-assembled polysomes synthesizing secretory protein. J. Cell Biol. 91, 545\u2013550 (1981).","journal-title":"J. Cell Biol."},{"key":"74404_CR7","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/nature19070","volume":"536","author":"D Schibich","year":"2016","unstructured":"Schibich, D. et al. Global profiling of SRP interaction with nascent polypeptides. Nature 536, 219\u2013223 (2016).","journal-title":"Nature"},{"key":"74404_CR8","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/0092-8674(91)90577-L","volume":"67","author":"BC Hann","year":"1991","unstructured":"Hann, B. C. & Walter, P. 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