Ribosome biogenesis
In prokaryotes, this process takes place in the cytoplasm with the transcription of many ribosome gene operons.
Most of the ribosomal proteins fall into various energy-consuming enzyme families including ATP-dependent RNA helicases, AAA-ATPases, GTPases, and kinases.
[2] Ribosome biogenesis is a very tightly regulated process, and it is closely linked to other cellular activities like growth and division.
There, the 35S pre-RNA is transcribed from ribosomal genes as a polycistronic transcript by RNA polymerase I and processed into the 18S, 5.8S, and 25S subunits of the rRNA.
[1] [3] Transcription of polymerase I starts with a Pol I initiation complex that binds to the rDNA promoter.
As the pol I transcript is produced, approximately 75 small nucleolar ribonucleoparticles (snoRNPs) facilitate the co-transcriptional covalent modifications of >100 rRNA residues.
[12] At this point in the ribosome biogenesis process, the 40S pre-ribosome already shows the “head” and “body” structures of the mature 40S subunit.
The final formation of the 40S subunit “beak” structure occurs after a phosphorylation and dephosphorylation event involving the Enp1-Ltv1-Rps3 complex and the kinase, Hrr25.
The subunit matures as it moves from the nucleolus to the cytoplasm and gradually the number of trans-acting factors are reduced.
Eight of these factors are directly involved with the processing of the 27S A3 pre-rRNA, which actually completes the formation of the mature 5’end of the 5.8S rRNA.
Subsequently, they bring areas of rRNA close together and promote the processing of pre-rRNA and the recruitment of ribosomal proteins.
The ring structure is attached to a flexible tail that happens to have a MIDAS (Metal ion-dependent adhesion site) tip.
Helicases and GTPases are also involved in the removal of assembly factors and the rearrangement of RNA to form the completed 60S subunit.
The rest of the large subunit ribosomal particles associate with the 60S unit and the remaining non-ribosomal assembly factors disassociate.
[3] The karyopherin Crm1 is the receptor for both ribosomal subunits and mediates export in a Ran-GTP dependent fashion.
To prevent this, cells have an active surveillance system to recognize damaged or defective ribosomes and target them for degradation.
[1] Pre-ribosomes that build up in the nucleus are destroyed by the exosome, which is a multisubunit complex with exonuclease activity.
Certain mutations in residues of the large ribosome subunit will actually result in RNA decay and thus degradation of the unit.
[3] Mutations in ribosome biogenesis are linked to several human ribosomopathy genetic diseases, including inherited bone marrow failure syndromes, which are characterized by a predisposition to cancer and a reduced number of blood cells.
