Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock.
Noncoding RNAs (ncRNAs) have recently been discovered to regulate mRNA transcription in trans, a role traditionally reserved for proteins. The breadth of ncRNAs as transacting transcriptional regulators and the diversity of signals to which they respond are only now becoming recognized. Here we show that human Alu RNA, transcribed from short interspersed elements (SINEs), is a transacting transcriptional repressor during the cellular heat shock response. Alu RNA blocks transcription by binding RNA polymerase II (Pol II) and entering complexes at promoters in vitro and in human cells. Transcriptional repression by Alu RNA involves two loosely structured domains that are modular, a property reminiscent of classical protein transcriptional regulators. Two other SINE RNAs, human scAlu RNA and mouse B1 RNA, also bind Pol II but do not repress transcription in vitro. These studies provide an explanation for why mouse cells harbor two major classes of SINEs, whereas human cells contain only one.
Mariner
Peter D
PD
Department of Chemistry and Biochemistry, University of Colorado at Boulder, 215 UCB, Boulder, CO 80309-0215, USA.
Walters
Ryan D
RD
Espinoza
Celso A
CA
Drullinger
Linda F
LF
Wagner
Stacey D
SD
Kugel
Jennifer F
JF
Goodrich
James A
JA
D020087:Alu Elements / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D051379:Mice; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020086:Short Interspersed Nucleotide Elements; D014158:Transcription, Genetic
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D022661:RNA, Untranslated; D012319:RNA Polymerase II