title: Transcriptional regulation by small RNAs at sequences downstream from 3' gene termini.
abstract: Transcriptome studies reveal many noncoding transcripts overlapping 3' gene termini. The function of these transcripts is unknown. Here we have characterized transcription at the progesterone receptor (PR) locus and identified noncoding transcripts that overlap the 3' end of the gene. Small RNAs complementary to sequences beyond the 3' terminus of PR mRNA modulated expression of PR, recruited argonaute 2 to a 3' noncoding transcript, altered occupancy of RNA polymerase II, induced chromatin changes at the PR promoter and affected responses to physiological stimuli. We found that the promoter and 3' terminal regions of the PR locus are in close proximity, providing a potential mechanism for RNA-mediated control of transcription over long genomic distances. These results extend the potential for small RNAs to regulate transcription to target sequences beyond the 3' termini of mRNA.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yue
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Schwartz
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chu
authors.forename: Scott T
authors.initials: ST
authors.lastname: Younger
authors.forename: Keith T
authors.initials: KT
authors.lastname: Gagnon
authors.forename: Sayda
authors.initials: S
authors.lastname: Elbashir
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Janowski
authors.forename: David R
authors.initials: DR
authors.lastname: Corey
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics* / Q000502:physiology; D020121:5' Untranslated Regions / Q000235:genetics; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D018390:Gene Targeting; D006801:Humans; D011487:Protein Conformation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020733:RNA, Small Cytoplasmic / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D019313:BRCA1 Protein; D002843:Chromatin; D018076:DNA, Complementary; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic