RNA-seeded membraneless bodies: Role of tandemly repeated RNA.

Abstract

Membraneless organelles (bodies, granules, etc.) are spatially distinct sub-nuclear and cytoplasmic foci involved in all the processes in a living cell, such as development, cell death, carcinogenesis, proliferation, and differentiation. Today the list of the membraneless organelles includes a wide spectrum of intranuclear and cytoplasmic bodies. Proteins with intrinsically disordered regions are the key players in the membraneless body assembly. However, recent data assume an important role of RNA molecules in the process of the liquid-liquid phase separation. High-level expression of RNA above a critical concentration threshold is mandatory to nucleate interactions with specific proteins and for seeding membraneless organelles. RNA components are considered by many authors as the principal determinants of organelle identity. Tandemly repeated (TR) DNA of big satellites (a TR family that includes centromeric and pericentromeric DNA sequences) was believed to be transcriptionally silent for a long period. Now we know about the TR transcription upregulation during gameto- and embryogenesis, carcinogenesis, stress response. In the review, we summarize the recent data about the involvement of TR RNA in the formation of nuclear membraneless granules, bodies, etc., with different functions being in some cases an initiator of the structures assembly. These RNP structures sequestrate and inactivate different proteins and transcripts. The TR induced sequestration is one of the key principles of nuclear architecture and genome functioning. Studying the role of the TR-based membraneless organelles in stress and disease will bring some new ideas for translational medicine.