A strategy for probing the function of noncoding RNAs finds a repressor of NFAT.
Noncoding RNA molecules (ncRNAs) have been implicated in numerous biological processes including transcriptional regulation and the modulation of protein function. Yet, in spite of the apparent abundance of ncRNA, little is known about the biological role of the projected thousands of ncRNA genes present in the human genome. To facilitate functional analysis of these RNAs, we have created an arrayed library of short hairpin RNAs (shRNAs) directed against 512 evolutionarily conserved putative ncRNAs and, via cell-based assays, we have begun to determine their roles in cellular pathways. Using this system, we have identified an ncRNA repressor of the nuclear factor of activated T cells (NFAT), which interacts with multiple proteins including members of the importin-beta superfamily and likely functions as a specific regulator of NFAT nuclear trafficking.
Willingham
A T
AT
Department of Chemistry, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Orth
A P
AP
Batalov
S
S
Peters
E C
EC
Wen
B G
BG
Aza-Blanc
P
P
Hogenesch
J B
JB
Schultz
P G
PG
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D034622:RNA Interference; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D028961:beta Karyopherins / Q000378:metabolism
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C503595:NRON long non-coding RNA, mouse; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; D028961:beta Karyopherins