title: Noncanonical microRNAs and endogenous siRNAs in normal and psoriatic human skin.
abstract: Noncanonical microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs) are key gene regulators in eukaryotes. Noncanonical miRNAs, which bypass part of the canonical miRNA biogenesis pathway, can originate from a variety of genomic loci, which include small nucleolar RNAs (snoRNAs), transfer RNAs (tRNAs) and introns, whereas endo-siRNAs can arise from repetitive elements, some of which are transposable. The roles of noncanonical miRNAs and endo-siRNAs in complex diseases have yet to be characterized. To investigate their potential expression and function in psoriasis, we carried out a comprehensive, genome-wide search for noncanonical miRNAs and endo-siRNAs in small RNA deep-sequencing data sets from normal and psoriatic human skin. By analyzing more than 670 million qualified reads from 67 small RNA libraries, we identified 21 novel, noncanonical miRNAs (3 snoRNA-derived and 2 tRNA-derived miRNAs and 16 miRtrons) and 39 novel endo-siRNAs that were expressed in skin. The expression of four novel small RNAs was validated by qRT-PCR in human skin, and their Argonaute association was confirmed by co-immunoprecipitation of ectopic small RNAs in HEK293 cells. Fifteen noncanonical miRNAs or endo-siRNAs were significantly differentially expressed in psoriatic-involved versus normal skin, including an Alu-short interspersed element-derived siRNA which was 17-fold up-regulated in psoriatic-involved skin. These and other differentially expressed small noncoding RNAs may function as regulators of gene expression in skin and potentially play a role in psoriasis pathogenesis.
authors.affiliation: Department of Computer Science and Engineering, Washington University, St Louis, MO 63130, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.forename: Cailin E
authors.initials: CE
authors.lastname: Joyce
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
authors.forename: Weixiong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002874:Chromosome Mapping; D056970:Co-Repressor Proteins; D017124:Conserved Sequence; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D015870:Gene Expression; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007438:Introns; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011565:Psoriasis / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D012867:Skin / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D056970:Co-Repressor Proteins; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; C514882:GON4L protein, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D020537:RNA, Small Nucleolar; D014157:Transcription Factors; D012343:RNA, Transfer