{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:51:23Z","timestamp":1790754683969,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Institute of Health Carlos III\/co-funding by FEDER","award":["PI16\/01074"],"award-info":[{"award-number":["PI16\/01074"]}]},{"name":"The Spanish Association for Cancer Research","award":["AECC, GCB120981SAN"],"award-info":[{"award-number":["AECC, GCB120981SAN"]}]},{"name":"The Samuel Sol\u00f3rzano Barruso foundation","award":["FS\/25-2015"],"award-info":[{"award-number":["FS\/25-2015"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>FAM46C<\/jats:italic>\n                    , frequently mutated in multiple myeloma (MM), has recently been shown to encode a non\u2010canonical poly(A) polymerase (ncPAP). However, its target mRNAs and its role in MM pathogenesis remain mostly unknown. Using CRISPR\u2010Cas9 technology and gene expression analysis, we found that the inactivation of FAM46C in MM down\u2010regulates immunoglobulins (Igs) and several mRNAs encoding ER\u2010resident proteins, including some involved in unfolded protein response and others that affect glycosylation. Interestingly, we show that FAM46C expression is induced during plasma cell (PC) differentiation and that Ig mRNAs encoding heavy and light chains are substrates of the ncPAP, as revealed by poly(A) tail\u2010length determination assays. The absence of the ncPAP results in Ig mRNA poly(A) tail\u2010shortening, leading to a reduction in mRNA and protein abundance. On the other hand, loss of FAM46C up\u2010regulates metastasis\u2010associated lncRNA MALAT1 and results in a sharp increase in the migration ability. This phenotype depends mainly on the activation of PI3K\/Rac1 signalling, which might have significant therapeutic implications. In conclusion, our results identify Ig mRNAs as targets of FAM46C, reveal an important function of this protein during PC maturation to increase antibody production and suggest that its role as a tumour suppressor might be related to the inhibition of myeloma cell migration.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.15078","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T07:56:17Z","timestamp":1583481377000},"page":"4171-4182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["FAM46C controls antibody production by the polyadenylation of immunoglobulin mRNAs and inhibits cell migration in multiple myeloma"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1414-6532","authenticated-orcid":false,"given":"Ana Bel\u00e9n","family":"Herrero","sequence":"first","affiliation":[{"name":"Haematology Department Institute of Biomedical Research of Salamanca (IBSAL) University Hospital of Salamanca Salamanca Spain"},{"name":"Cancer Research Center\u2010IBMCC (USAL\u2010CSIC) Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Quwaider","sequence":"additional","affiliation":[{"name":"Haematology Department Institute of Biomedical Research of Salamanca (IBSAL) University Hospital of Salamanca Salamanca Spain"},{"name":"Cancer Research Center\u2010IBMCC (USAL\u2010CSIC) Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-8599","authenticated-orcid":false,"given":"Luis Antonio","family":"Corchete","sequence":"additional","affiliation":[{"name":"Haematology Department Institute of Biomedical Research of Salamanca (IBSAL) University Hospital of Salamanca Salamanca Spain"},{"name":"Cancer Research Center\u2010IBMCC (USAL\u2010CSIC) Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Victoria","family":"Mateos","sequence":"additional","affiliation":[{"name":"Haematology Department Institute of Biomedical Research of Salamanca (IBSAL) University Hospital of Salamanca Salamanca Spain"},{"name":"Cancer Research Center\u2010IBMCC (USAL\u2010CSIC) Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Garc\u00eda\u2010Sanz","sequence":"additional","affiliation":[{"name":"Haematology Department Institute of Biomedical Research of Salamanca (IBSAL) University Hospital of Salamanca Salamanca Spain"},{"name":"Cancer Research Center\u2010IBMCC (USAL\u2010CSIC) Salamanca Spain"},{"name":"Center for Biomedical Research in Network of Cancer (CIBERONC) Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma C.","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Haematology Department Institute of Biomedical Research of Salamanca (IBSAL) University Hospital of Salamanca Salamanca 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