title: IsomiR expression profiles in human lymphoblastoid cell lines exhibit population and gender dependencies.
abstract: For many years it was believed that each mature microRNA (miRNA) existed as a single entity with fixed endpoints and a 'static' and unchangeable primary sequence. However, recent evidence suggests that mature miRNAs are more 'dynamic' and that each miRNA precursor arm gives rise to multiple isoforms, the isomiRs. Here we report on our identification of numerous and abundant isomiRs in the lymphoblastoid cell lines (LCLs) of 452 men and women from five different population groups. Unexpectedly, we find that these isomiRs exhibit an expression profile that is population-dependent and gender-dependent. This is important as it indicates that the LCLs of each gender/population combination have their own unique collection of mature miRNA transcripts. Moreover, each identified isomiR has its own characteristic abundance that remains consistent across biological replicates indicating that these are not degradation products. The primary sequences of identified isomiRs differ from the known miRBase miRNA either at their 5´-endpoint (leads to a different 'seed' sequence and suggests a different targetome), their 3´-endpoint, or both simultaneously. Our analysis of Argonaute PAR-CLIP data from LCLs supports the association of many of these newly identified isomiRs with the Argonaute silencing complex and thus their functional roles through participation in the RNA interference pathway.
authors.affiliation: Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Phillipe
authors.initials: P
authors.lastname: Loher
authors.affiliation: Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Londin
authors.affiliation: Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Isidore
authors.initials: I
authors.lastname: Rigoutsos
mesh_terms: D001741:Black or African American / Q000235:genetics*; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D005060:Europe / Q000208:ethnology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009549:Nigeria / Q000208:ethnology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D014589:Utah / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: D060565:Argonaute Proteins; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012322:RNA Precursors