Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre
Authors: Patrick McClanahan
Ezgi Hacisuleyman
John L Rinn
David G Hendrickson
Jesse Engreitz
Cole Trapnell
David R Kelley
Richard Flavell
Eric S Lander
Michael Morse
Harvey F Lodish
Jorge Henao-Mejia
Arjun Raj
Loyal A Goff
Martin Sauvageau
Mitch Guttman
Adam Williams
Lei Sun
Journal: Nature Structural & Molecular Biology (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: RNA; long noncoding RNA; lncRNA; nuclear matrix; Firre
Affiliations: 1] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [3] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA. [4]., 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA. [3] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [4]., 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA., Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA., Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA., Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA., Department of Biology, California Institute of Technology, Pasadena, California, USA., 1] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., 1] Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA., 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA. [3] Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Abstract:  RNA, including long noncoding RNA (lncRNA), is known to be an abundant and important structural component of the nuclear matrix. However, the molecular identities, functional roles and localization dynamics of lncRNAs that influence nuclear architecture remain poorly understood. Here, we describe one lncRNA, Firre, that interacts with the nuclear-matrix factor hnRNPU through a 156-bp repeating sequence and localizes across an ~5-Mb domain on the X chromosome. We further observed Firre localization across five distinct trans-chromosomal loci, which reside in spatial proximity to the Firre genomic locus on the X chromosome. Both genetic deletion of the Firre locus and knockdown of hnRNPU resulted in loss of colocalization of these trans-chromosomal interacting loci. Thus, our data suggest a model in which lncRNAs such as Firre can interface with and modulate nuclear architecture across chromosomes. 

Retracted: No

PubPeer comments:
 Figure 6a has an area of sharp transition. Could the authors provide an original uncropped scan? A reader on social media agrees that this may be an undisclosed splice. *** Inverse, contrast enhanced ![file] *** Original ![file] , 
 #1 Uncropped versions of blots for Fig 6a and 6b were published with the paper, as Supplementary Figure 7. See here: https: www.nature.com articles nsmb.2764 figures 14 Some blots were not included (e.g., for 6a panel 5, and 6b panel 3). For the panel you highlighted, it is not clear to me that the uncropped version shown in Supp Fig 7 is the same blot, as the pattern of swirling background noise seems different. E.g., in Fig 6a, lane 2 seems to be a locally brighter than lanes 3-4, whereas the reverse is true in the uncropped blot of Supp Fig 7. , 
 Thank you for keeping data reproducibility in check! NSMB also requires all raw images for westerns. Can you please look at Supplemental FIgure 7 which is all the raw blots? It is possible that it was unintentionally spliced from these raw blots and not reported. In this case the gel is not controlled for relative abundance to other proteins rather binary calls across lanes. In other words if there was no real input band the other bands would have likely had to been spliced in too -- and are clearly not from Supplemental figure 7. Nonetheless if it is indeed spliced we will report that immediately. Thanks again! John Rinn , 
 #2 and #3 Thank you both for pointing me to the supplemental figure, which you are correct in assuming I had not reviewed. I will leave it to the authors to pursue this matter as they wish. ,