Emerging mechanisms of long noncoding RNA function during normal and malignant hematopoiesis

Long noncoding RNAs (lncRNAs) are increasingly recognized as vital components of gene programs controlling cell differentiation and function. Central to their functions is an ability to act as scaffolds or as decoys that recruit or sequester effector proteins from their DNA, RNA, or protein targets. lncRNA-modulated effectors include regulators of transcription, chromatin organization, RNA processing, and translation, such that lncRNAs can influence gene expression at multiple levels.

Researchers from Harvard University and the Whitehead Institute for Biomedical Research review the current understanding of how lncRNAs help coordinate gene expression to modulate cell fate in the hematopoietic system. They focus on a growing number of mechanistic studies to synthesize emerging principles of lncRNA function, emphasizing how they facilitate diversification of gene programming during development. The researchers also survey how disrupted lncRNA function can contribute to malignant transformation, highlighting opportunities for therapeutic intervention in specific myeloid and lymphoid cancers. Finally, they discuss challenges and prospects for further elucidation of lncRNA mechanisms.

 Many lncRNAs scaffold proteins to their targetslncRNA

(A) Xist directs X chromosome inactivation across eutherian females. RNA FISH image shows focal retention of Xist transcripts (red; blue fluorescence demarks the nucleus). (B) lincRNA-EPS represses apoptotic/inflammatory response genes. RNA FISH image shows nuclear diffusion of lincRNA-EPS transcripts (red). (C) LUNAR1 sustains oncogenic IGF1R activation in cis. (D) Bloodlinc potentiates the terminal erythropoiesis gene program. RNA FISH image shows nuclear diffusion of Bloodlinc molecules.

Alvarez-Dominguez JR, Lodish HF. (2017) Emerging mechanisms of long noncoding RNA function during normal and malignant hematopoiesis. Blood [Epub ahead of print]. [abstract]

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