Meta-Biol

• Pathways

Human ribosomal RNAs (rRNAs) contain about 200 residues that are enzymatically modified after transcription in the nucleolus (Maden and Khan 1977, Maden 1988, Maden and Hughes 1997, reviewed in Hernandez-Verdun et al. 2010, Boschi-Muller and Motorin 2013). The modified residues occur in regions of the rRNAs that are located in functionally important parts of the ribosome, notably in the A and P peptidyl transfer sites, the polypeptide exit tunnel, and intersubunit contacts (Polikanov et al. 2015, reviewed in Decatur and Fournier 2002, Chow et al. 2007, Sharma and Lafontaine 2015). The two most common modifications are pseudouridines and 2'-O-methylribonucleotides. Formation of pseudouridine from encoded uridine is catalyzed by box H/ACA small nucleolar ribonucleoprotein (snoRNP) complexes (reviewed in Hamma and Ferre-D'Amare 2010, Watkins and Bohnsack 2011, Ge and Yu 2013, Kierzek et al. 2014, Yu and Meier 2014) and methylation of the hydroxyl group of the 2' carbon is catalyzed by box C/D snoRNPs (Kiss-Laszlo et al. 1996, Lapinaite et al. 2013, reviewed in Watkins and Bohnsack 2011). The snoRNP complexes contain common sets of protein subunits and unique snoRNAs that guide each complex to its target nucleotide of the rRNA by base-pairing between the snoRNA and the rRNA (reviewed in Henras et al. 2004, Watkins and Bohnsack 2011). Other modifications of rRNA include 5-methylcytidine (reviewed in Squires and Preiss 2010), 1-methylpseudouridine, 7-methylguanosine, 6-dimethyladenosine, and 4-acetylcytidine (reviewed in Sharma and Lafontaine 2015). In yeast most modifications are introduced co-transcriptionally (Kos and Tollervey 2010, reviewed in Turowski and Tollervey 2015), however the order of modification events and pre-rRNA cleavage events is not well characterized.

Each eukaryotic cytosolic ribosome contains 4 molecules of RNA: 28S rRNA (25S rRNA in yeast), 5.8S rRNA, and 5S rRNA in the 60S subunit and 18S rRNA in the 40S subunit. The 18S rRNA, 5.8S rRNA, and 28S rRNA are produced by endonucleolytic and exonucleolytic processing of a single 47S precursor (pre-rRNA) (reviewed in Henras et al. 2015). Transcription of ribosomal RNA genes, processing of pre-rRNA, and assembly of precursor 60S and 40S subunits occur in the nucleolus (reviewed in Hernandez-Verdun et al. 2010), with a few late reactions occurring in the cytosol. Within the nucleolus non-transcribed DNA and inactive polymerase complexes are located in the fibrillar center, active DNA polymerase I transcription occurs at the interface between the fibrillar center and the dense fibrillar component, early processing of pre-rRNA occurs in the dense fibrillar component, and late processing of pre-rRNA occurs in the granular component (Stanek et al. 2001).
Processed ribosomal RNA contains many modified nucleotides which are generated by enzymes acting on encoded nucleotides contained in the precursor rRNA (reviewed in Boschi-Muller and Motorin 2013). The most numerous modifications are pseudouridine residues and 2'-O-methylribonucleotides. Pseudouridylation is guided by base pairing between the precursor rRNA and a small nucleolar RNA (snoRNA) in a Box C/D snoRNP (reviewed in Henras et al 2004, Yu and Meier 2014). Similarly, 2'-O-methylation is guided by base pairing between the precursor rRNA and a snoRNA in a Box H/ACA snoRNP (reviewed in Henras et al. 2004, Hamma and Ferre-D'Amare 2010). Other modifications include N(1)-methylpseudouridine, 5-methylcytosine, 7-methylguanosine, 6-dimethyladenosine, and 4-acetylcytidine. Modification of nucleotides occur as the pre-rRNA is being cleaved. However, the order of cleavage and modification steps is not clear so these two processes are presented separately here. Defects in ribosome biogenesis factors can cause disease (reviewed in Freed et al. 2010).
Mitochondrial ribosomes are completely distinct from cytoplasmic ribosomes, having different protein subunits and 12S rRNA and 16S rRNA. The mitochondrial rRNAs are encoded in the mitochondrial genome and are produced by processing of a long H strand transcript. Specific residues in the rRNAs are modified by enzymes to yield 5 different types of modified nucleotides:

This superpathway encompasses the processes by which RNA transcription products are further modified covalently and non-covalently to yield their mature forms, and the regulation of these processes. Annotated pathways include ones for capping, splicing, and 3'-cleavage and polyadenylation to yield mature mRNA molecules that are exported from the nucleus (Hocine et al. 2010). mRNA editing and nonsense-mediated decay are also annotated. Processes leading to mRNA breakdown are described: deadenylation-dependent mRNA decay, microRNA-mediated RNA cleavage, and regulation of mRNA stability by proteins that bind AU-rich elements.psnRNP assembly is also annotated here.

The aminoacylation of mature tRNAs is annotated in the "Metabolism of proteins" superpathway, as a part of "Translation".