Biological complexity: controls of nucleolus (Introduction)

by David Turell , Friday, July 30, 2021, 15:14 (1212 days ago) @ David Turell

A vital part of a nucleus has no membrane to separate itself, but it totally controlled by a liquid liquid phase transition:

https://science.sciencemag.org/content/373/6554/486

"Intracellular organelles that lack a membrane boundary are often formed through liquid-liquid phase separation. The biophysical properties of such structures are linked to their physiological functions and involvement in diseases. Most of these organelles contain RNA molecules that associate with RNA binding proteins (RBPs) to control intracellular phase separation (1). Specific long noncoding RNAs (lncRNAs) are especially important in the architecture of membraneless organelles (2). On page 547 of this issue, Wu et al. (3) provide a mechanistic understanding of how lncRNAs modulate the biophysical properties of phase-separated nucleolar subdomains of the nucleus, where ribosome biogenesis takes place.

"The nucleolus is the largest membraneless subnuclear organelle and serves as a location for ribosome production, a critical determinant of protein synthesis capacity. It comprises multilayered phase-separated subdomains that possess distinct biophysical properties: fibrillar centers (FCs) that contain the tandemly repeated ribosomal RNA (rRNA) gene cluster [or ribosomal DNA (rDNA)]; the dense fibrillar component (DFC) that surrounds FCs; and the granular component (GC) that includes dozens of FC/DFC units (4). The organized multilayered structure of the nucleolus is thought to ensure efficient ribosome biogenesis. This is initiated by rDNA transcription by RNA polymerase I (Pol I) to generate pre-rRNA at the border between the FC and DFC, subsequent pre-rRNA processing in the DFC, and later events, including ribonucleo-protein (RNP) assembly into the ribosomal subunits in the GC.

"Wu et al. focused on a human-specific nucleolar lncRNA called SLERT (a box H/ACA small nucleolar RNA–ended long noncoding RNA that enhances pre-rRNA transcription) that is located in the DFC. The importance of SLERT was noted by the reduced size and liquidity of the FC/DFC in the absence of the lncRNA (5). SLERT associates with the nucleolar RNA helicase DDX21 (DExD-box helicase 21), which regulates transcription by Pol I. Through in vitro reconstitution and in vivo experiments, Wu et al. demonstrate a role of DDX21 in the architecture and biophysical properties of the FC/DFC and in the regulation of Pol I–mediated transcription. The authors also show how SLERT modulates two distinct DDX21 functions."

Explanatory summary:

https://science.sciencemag.org/content/373/6554/529.15?utm_campaign=twis_sci_2021-07-29...

"The nucleolus is a multilayered, membraneless nuclear condensate in which DNA polymerase I (Pol I)–mediated ribosomal DNA (rDNA) transcription and pre-rRNA processing occur in fibrillar center and dense fibrillar component (FC/DFC) units. How the biophysical properties of the nucleolus are regulated has remained elusive. Wu et al. found that the RNA helicase DDX21 forms a shell coating each FC/DFC unit in the nucleolus (see the Perspective by Yamazaki and Hirose). The authors found that a long noncoding RNA called SLERT facilitates the transition from the open to the closed configuration of the helicase using a chaperonelike mechanism. DDX21 in the closed conformation forms loose clusters that confer the FC/DFC unit sufficient liquidity and space required for Pol I processivity. In addition, DDX21 within the loose clusters cannot approach and wrap rDNA, thus licensing rDNA for transcription."

Comment: One does not need to fully understand the architecture described to recognize the extreme complexity. Note lots of 'junk DNA' is required. Evolution produced a purposeful design in 80% in our genome. There is no evidence of any random or chance development. It must be seen as designed