The long noncoding RNA SPRIGHTLY acts as an intranuclear organizing hub for pre-mRNA molecules

Science Advances
Bongyong LeeRanjan J Perera

Abstract

Molecular mechanisms by which long noncoding RNA (lncRNA) molecules may influence cancerous condition are poorly understood. The aberrant expression of SPRIGHTLY lncRNA, encoded within the drosophila gene homolog Sprouty-4 intron, is correlated with a variety of cancers, including human melanomas. We demonstrate by SHAPE-seq and dChIRP that SPRIGHTLY RNA secondary structure has a core pseudoknotted domain. This lncRNA interacts with the intronic regions of six pre-mRNAs: SOX5, SMYD3, SND1, MEOX2, DCTN6, and RASAL2, all of which have cancer-related functions. Hemizygous knockout of SPRIGHTLY by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 in melanoma cells significantly decreases SPRIGHTLY lncRNA levels, simultaneously decreases the levels of its interacting pre-mRNA molecules, and decreases anchorage-independent growth rate of cells and the rate of in vivo tumor growth in mouse xenografts. These results provide the first demonstration of an lncRNA's three-dimensional coordinating role in facilitating cancer-related gene expression in human melanomas.

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Citations

Feb 28, 2018·Cell Proliferation·Zheng LiWilliam Ka Kei Wu
Jul 25, 2019·Journal of Molecular Cell Biology·Alisha N Jones, Michael Sattler
Jun 17, 2020·Wiley Interdisciplinary Reviews. RNA·Fatu Badiane MarkeyMona Batish
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Feb 26, 2021·Frontiers in Oncology·Animesh RayRanjan J Perera
Apr 13, 2021·Neuro-oncology·Keisuke KatsushimaRanjan J Perera
Apr 27, 2021·Technology in Cancer Research & Treatment·Xiaotao SuChao Qin
Aug 3, 2021·Journal of Parkinson's Disease·Ida MannaAldo Quattrone

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Methods Mentioned

BETA
SHAPE-seq
pull down
pulldown
antisense
PCR
smFISH
xenografts
xenograft
antisense oligonucleotides
RNA-Seq

Software Mentioned

BLAT
Bowtie
MACS2
MATLAB
VARNA
SPRIGHTLY
Cutadapt
Spats
GeneMANIA
dChIRP

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