XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure.
The XIST gene is implicated in X chromosome inactivation, yet the RNA contains no apparent open reading frame. An accumulation of XIST RNA is observed near its site of transcription, the inactive X chromosome (Xi). A series of molecular cytogenetic studies comparing properties of XIST RNA to other protein coding RNAs, support a critical distinction for XIST RNA; XIST does not concentrate at Xi simply because it is transcribed and processed there. Most notably, morphometric and 3-D analysis reveals that XIST RNA and Xi are coincident in 2- and 3-D space; hence, the XIST RNA essentially paints Xi. Several results indicate that the XIST RNA accumulation has two components, a minor one associated with transcription and processing, and a spliced major component, which stably associates with Xi. Upon transcriptional inhibition the major spliced component remains in the nucleus and often encircles the extra-prominent heterochromatic Barr body. The continually transcribed XIST gene and its polyadenylated RNA consistently localize to a nuclear region devoid of splicing factor/poly A RNA rich domains. XIST RNA remains with the nuclear matrix fraction after removal of chromosomal DNA. XIST RNA is released from its association with Xi during mitosis, but shows a unique highly particulate distribution. Collective results indicate that XIST RNA may be an architectural element of the interphase chromosome territory, possibly a component of nonchromatin nuclear structure that specifically associates with Xi. XIST RNA is a novel nuclear RNA which potentially provides a specific precedent for RNA involvement in nuclear structure and cis-limited gene regulation via higher-order chromatin packaging.
Clemson
C M
CM
Department of Cell Biology, University of Massachusetts Medical Center, Worcester 01655, USA.
McNeil
J A
JA
Willard
H F
HF
Lawrence
J B
JB
D002453:Cell Cycle; D002460:Cell Line; D002843:Chromatin / Q000502:physiology / Q000648:ultrastructure; D003094:Collagen / Q000096:biosynthesis; D015342:DNA Probes; D004171:Diploidy; D005260:Female; D016193:G1 Phase; D015723:Gene Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008938:Mitosis; D008961:Models, Structural; D015530:Nuclear Matrix / Q000502:physiology / Q000648:ultrastructure; D012313:RNA / Q000032:analysis / Q000096:biosynthesis*; D012326:RNA Splicing; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014960:X Chromosome
D002843:Chromatin; D015342:DNA Probes; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA; D012313:RNA; D003094:Collagen