Hold on to your friends: Dedicated chaperones of ribosomal proteins

Abstract

Eukaryotic ribosomes are assembled from their components, the ribosomal RNAs and ribosomal proteins, in a tremendously complex, multi-step process, which primarily takes place in the nuclear compartment. Therefore, most ribosomal proteins have to travel from the cytoplasm to their incorporation site on pre-ribosomes within the nucleus. However, due to their particular characteristics, such as a highly basic amino acid composition and the presence of unstructured extensions, ribosomal proteins are especially prone to aggregation and degradation in their unassembled state, hence specific mechanisms must operate to ensure their safe delivery. Recent studies have uncovered a group of proteins, termed dedicated chaperones, specialized in accompanying and guarding individual ribosomal proteins. In this essay, we review how these dedicated chaperones utilize different folds to interact with their ribosomal protein clients and how they ensure their soluble expression and interconnect their intracellular transport with their efficient assembly into pre-ribosomes.

Placeholder factors in ribosome biogenesis: please, pave my way

“…In agreement with this, recombinant S14 from E. coli showed poor solubility unless it is co-expressed with Fap7 185; moreover, depletion of Fap7 causes a strong decrease in the in vivo protein levels of S14 in S. cerevisiae 171. However, there is so far no evidence for co-translational capturing of S14 by Fap7 (discussed in 151). …”

“…So far, seven specific systems, composed of a dedicated chaperone or an escortin and an r-protein, have been reported in yeast, a list that may still be far from being completed: Acl4•L4, Bcp1•L23, Rrb1•L3, Sqt1•L10, Syo1•L5•L11, Tsr2•S26 and Yar1•S3 (for a review, see 151). For most of them, the binding sites of the chaperone on the respective r-protein have been mapped, and for several of them structural information is also available.…”

“…Following this cytoplasmic recognition, Rrb1 then accompanies L3 to its assembly site on early nucleolar pre-60S r-particles 78152157. Unfortunately, no structural data have so far been reported for this interaction, although it has been speculated to occur in a similar manner as that between Sqt1, another WD-repeat protein, and its specific partner, the r-protein L10 (see below) 151. Despite this issue, it is clear that the interaction of L3 with Rrb1 is mutually exclusive with the ribosomal interaction of L3.…”

“…(ii) Moreover, mutations in the RPL10 gene have been identified in patients of T-cell acute lymphoblastic leukaemia and they also seem to impair the efficient release of Tif6 and Nmd3 from cytoplasmic pre-60S r-particles (see 206, and references therein). (iii) The Syndrome 5q- seems to be caused by a RPS14 haploinsuficiency (reviewed in 207), thus, it is reasonable to imagine that certain loss-of-function mutations in FAP7 could be identified in the future as linked to this disease, in a similar manner as mutations in RPS26 or its escortin TSR2 have been linked to the Diamond-Blackfan Anemia (discussed in 151). (iv) Some mutations in dyskerin (human Cbf5) related to X-linked dyskeratosis congenita lead to the destabilization of the interaction of the mutant variant of dyskerin with its placeholder SHQ1 187.…”

When a ribosomal protein grows up - the ribosome assembly path of Rps3

“…Although the details will certainly vary between different r-proteins, similar mechanisms as utilized by Rps3 may also be employed by other r-proteins. The engagement of dedicated chaperones was also reported for some other r-proteins in recent years, and more dedicated r-protein chaperones might still await their discovery 21112131415161718192021.…”