Regulating gene expression through RNA nuclear retention.
Multiple mechanisms have evolved to regulate the eukaryotic genome. We have identified CTN-RNA, a mouse tissue-specific approximately 8 kb nuclear-retained poly(A)+ RNA that regulates the level of its protein-coding partner. CTN-RNA is transcribed from the protein-coding mouse cationic amino acid transporter 2 (mCAT2) gene through alternative promoter and poly(A) site usage. CTN-RNA is diffusely distributed in nuclei and is also localized to paraspeckles. The 3'UTR of CTN-RNA contains elements for adenosine-to-inosine editing, involved in its nuclear retention. Interestingly, knockdown of CTN-RNA also downregulates mCAT2 mRNA. Under stress, CTN-RNA is posttranscriptionally cleaved to produce protein-coding mCAT2 mRNA. Our findings reveal a role of the cell nucleus in harboring RNA molecules that are not immediately needed to produce proteins but whose cytoplasmic presence is rapidly required upon physiologic stress. This mechanism of action highlights an important paradigm for the role of a nuclear-retained stable RNA transcript in regulating gene expression.
Prasanth
Kannanganattu V
KV
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Prasanth
Supriya G
SG
Xuan
Zhenyu
Z
Hearn
Stephen
S
Freier
Susan M
SM
Bennett
C Frank
CF
Zhang
Michael Q
MQ
Spector
David L
DL
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D002458:Cell Fractionation; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002875:Chromosomes; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016678:Genome; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011061:Poly A / Q000235:genetics*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D017393:RNA Editing; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis; D012342:RNA, Small Nuclear / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D027202:Cationic Amino Acid Transporter 2; D008070:Lipopolysaccharides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012342:RNA, Small Nuclear; D049452:Green Fluorescent Proteins; D011061:Poly A; D012313:RNA; D007371:Interferon-gamma