The daunting task of modifying ribosomal RNA

Abstract

One of the most basic tasks of every cell is the synthesis of ribosomes, yet the process is so complex that we are only beginning to comprehend it. In human cells, the final product contains four RNAs and 79 proteins forming a large ribonucleoprotein, the ribosome. About twice as many factors are involved in assembly of these protein synthesizing machines. Additionally, some 200 small nucleolar ribonucleoproteins (snoRNPs) function in the modification of pre-ribosomal RNA (pre-rRNA) at a similar number of ribonucleotides. Modification is essential for proper function and biogenesis of ribosomes (Decatur and Fournier 2002; Sloan et al. 2016). While abrogation of individual modifications has little to no measurable effects, removal of a combination of modifications or of all causes severe to lethal effects. Modifications mostly cluster around the functional centers of the ribosome and some modifications are important for ribosome assembly. The subject of this perspective is to raise awareness to how modification at so many sites can be achieved while the pre-rRNA is being processed, folded and re-folded, and assembled with ribosomal proteins to yield the pre-ribosomal subunits in the nucleolus (Baßler and Hurt 2019). This is not a comprehensive review but a simplification of complex issues providing access to the general reader.

Viscoelasticity and advective flow of RNA underlies nucleolar form and function

“… 23 As nascent rRNA is transcribed, enzymes such as fibrillarin (FBL, part of the C/D Box snoRNP complex) localize to the DFC to promote initial rRNA modification and cleavage steps. 24 , 25 Finally, the GC contains various proteins that assist in further rRNA processing and binding to ribosomal proteins (r-proteins), ultimately forming nearly complete RSUs, which then move into the nucleoplasm and the cytoplasm. 22 , 26 , 27 The size of the compartments suggests that rRNA processing and folding in the GC are the ratelimiting steps for RSU assembly.…”

Comprehensive profiling of rRNA-derived small RNAs in Arabidopsis thaliana using rsRNAfinder pipeline

“…Based on the modification data and annotated snoRNAs of 25S, 5.8S, and 18S obtained from snOPY, we observed that SnoR12–1b snoRNA guides the most modifications in 25S rRNA, primarily associated with methylation rather than pseudouridylation. On the other hand, it is also important to note that there is a lack of information modification sites of rRNA in public repositories [ 27 , 16 , 28 ]. However, ongoing efforts are underway to identify modifications across all existing rRNA types.…”

Non-Coding RNAs in Human Cancer and Other Diseases: Overview of the Diagnostic Potential

“…For example, nascent pre-rRNA molecules undergo, after transcription, a series of processing steps to produce the mature rRNA molecule. Prior to cleavage by exoand endonucleases, the pre-rRNA molecule undergoes a series of nucleoside modifications by methylations and pseudouridylations that is guided by snoRNAs [57]. snoRNAs may serve as miRNAs precursors, e.g., snoRNA called ACA45 can be processed into a mature miRNA of 21 nt length by the RNAse III endoribonuclease dicer.…”