RRP36

RRP36 (Rrp36p) is an essential nucleolar protein required for the early pre-rRNA cleavages that generate the 18S rRNA and the small (40S) ribosomal subunit (PMID:20038530). It associates with 90S and pre-40S preribosomal particles, and its depletion blocks early cleavages of the 35S pre-rRNA and rapidly depletes mature 18S rRNA (PMID:20038530). Within the SSU-processome, RRP36 is recruited as a function of the UTP-A and UTP-B assembly modules, while it is itself dispensable for incorporation of the UTP-A, UTP-B, UTP-C subcomplexes and the U3 snoRNP, placing it downstream of these modules in the assembly hierarchy (PMID:20038530). RRP36 directly contacts the β-propeller domain of Rrp9 (U3-55K), and disruption of this interface specifically impairs cleavage at sites A1 and A2, linking the Rrp9–RRP36 contact to processome function (PMID:31996908). This role in early pre-rRNA processing is conserved to the human orthologue (C6orf153/RRP36) (PMID:20038530).

1. 2009 High

   Established that Rrp36p is a nucleolar factor functionally required for small subunit biogenesis, answering whether the uncharacterized protein had a defined role in ribosome assembly.

   Evidence Conditional depletion, northern blotting of pre-rRNA, sucrose-gradient co-fractionation, and nucleolar localization in yeast

   PMID:20038530

   Open questions at the time

   • Molecular activity of Rrp36 during cleavage not defined
   • Does not establish whether Rrp36 acts catalytically or as a scaffold
2. 2009 High

   Positioned Rrp36 in the 90S preribosome assembly hierarchy, resolving which modules license its recruitment versus which depend on it.

   Evidence Reciprocal depletion epistasis with UTP-A, UTP-B, UTP-C, U3 snoRNP and Rrp5p followed by co-fractionation and western blotting

   PMID:20038530

   Open questions at the time

   • Direct binding partner mediating UTP-A/UTP-B-dependent recruitment not identified at this stage
   • Structural basis of incorporation unknown
3. 2009 Medium

   Tested whether the processing role is conserved beyond yeast, addressing relevance of the yeast findings to human ribosome biogenesis.

   Evidence siRNA knockdown of human C6orf153/RRP36 in HeLa cells with northern analysis of pre-rRNA intermediates

   PMID:20038530

   Open questions at the time

   • Human data limited to processing readout
   • Human interaction partners and assembly context not mapped
4. 2020 Medium

   Identified a direct molecular contact (Rrp9 β-propeller) explaining how Rrp36 is integrated into the SSU-processome and contributes to specific cleavages.

   Evidence Direct interaction assay, site-directed mutagenesis of Rrp9 (R289A), and northern analysis of A1/A2 cleavage in yeast

   PMID:31996908

   Open questions at the time

   • Single lab study
   • Atomic structure of the Rrp36-Rrp9 interface not solved
   • Whether this contact alone accounts for UTP-A/UTP-B-dependent recruitment unresolved

• The biochemical activity of RRP36 within the processome — whether it directly facilitates cleavage chemistry, conformational rearrangement, or substrate positioning — remains undefined.
• No catalytic activity assigned
• No structural model of RRP36 in the processome
• Human interactome not characterized