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N-terminal acetylation shapes protein fate during protein biosynthesis at the ribosome. Here the authors show that the NatA enzyme forms dynamic multi-factor complexes at the ribosome, acting as an interaction hub that coordinates cotranslational protein maturation.

Eukaryotic ribosomal proteins contain nuclear localization signals (NLSs) that their bacterial counterparts lack. Here the authors compare homologous proteins from bacterial and eukaryotic ribosomes to show how NLSs could emerge in the course of evolution, and use this knowledge to identify novel NLSs.

The GroEL/ES chaperonin can act during protein synthesis to promote folding. Here, Roeselová et al. show how GroEL captures, remodels and sequesters nascent proteins in its central chamber, while they remain tethered to the ribosome.

Ribosome stalling during translation threatens proteostasis and requires targeted clearance of nascent chains. Here, the authors show how the yeast RQC complex recruits Cdc48 via Ltn1 and Rqc1 to extract ubiquitylated peptides, revealing the structural basis of stalled nascent chain removal.

Cotranslational N-terminal methionine excision and acetylation of eukaryotic proteins on ribosomes is coordinated by the nascent polypeptide-associated complex.

Assembly of functional ribosomal subunits is aided by dedicated assembly factors. Here, the authors show that the Reh1 is positioned in the polypeptide exit tunnel of 80S ribosomes, suggesting that the growing polypeptide chain displaces Reh1 during first round of translation.

Ribosome ubiquitination regulates HAC1 mRNA processing during the unfolded protein response. Here, the authors show that the SCFGrr1 complex promotes HAC1 mRNA splicing and translation by degrading the deubiquitinating enzyme Ubp3, thereby maintaining eS7A monoubiquitination to facilitate HAC1i translation.

The initiation of protein synthesis requires the eukaryotic translation initiation factor (eIF) 2, which uses energy from the hydrolysis of GTP. Another factor, eIF5, accelerates the GTP-hydrolysing activity of eIF2. Here, two other roles for eIF5 have been defined. One involves stabilizing GDP, the product of GTP hydrolysis, on eIF2. In its other role, eIF5 works with phosphorylated eIF2 to inhibit the guanine-nucleotide exchange factor eIF2B. These results clarify our understanding of how the initiation of translation is regulated.

Initiation factors eIF1 and eIF1A are key determinants of ribosomal scanning and initiation-codon selection during translation initiation. The structure of Tetrahymena thermophila 40S ribosome in complex with eIF1 and eIF1A reveals the conformational changes that accompany initiation-factor binding and provides new insights into the mechanism of start-codon recognition.

The central dogma of molecular biology requires many proteins, but how these proteins arose during evolution remains unclear. Here, authors reveal that a subset of RNA polymerases and ribosomal proteins featuring four distinct β-barrel folds diversified from a common ancestor.

Yelland et al. use yeast genetics and cryo-EM to show how 2′-O-methylation on a single rRNA base gates the assembly of the ribosome via regulating interaction with the essential GTPase Nog2.

Structural studies of the ribosome-associated endoplasmic reticulum translocon complex based on cryo-electron tomography and molecular modelling reveal multiple intermediate states and interactions between the components of the complex and its cofactors.

Here, structures of archaeal ribosome show details of ribosomal proteins and leaderless mRNAs binding to the small subunit, suggesting a positive role of eS26 in leaderless mRNAs translation and possible evolutionary routes from archaeal to eukaryotic translation.

Xenopus egg extracts constitute a cell-like system for studying biochemical reactions. Here Chen and co-workers show that extract protein synthesis and degradation are differently affected by cytoplasmic concentration and viscosity.

The accuracy of eukaryotic ribosome translocation relies on eukaryote-specific elements of the 80S ribosome, elongation factor 2 and transfer RNAs, all of which contribute to the maintenance of the messenger RNA reading frame.

Developments in cryo-EM sample preparation and data collection are pivotal for structure determination. Fromm et al. present a 1.55 Å structure of the translating bacterial ribosome that provides new insights on its function and may allow for more precise structure-based drug design.

Mitochondrial ribosomes (mitoribosomes) are characterized by a distinct architecture and thus biogenesis pathway. Here, cryo-EM structures of mitoribosome large subunit assembly intermediates elucidate final steps of 16 S rRNA folding, methylation and peptidyl transferase centre (PTC) completion, as well as functions of several mitoribosome assembly factors.

Maturation of the ribosomal peptidyl transferase center (PTC) is mediated by universally conserved GTPases. Here, cryo-EM structures of mitochondrial ribosomal large subunit assembly intermediates and of mature ribosomes offer insight into the roles of several assembly factors, including GTPBP6’s role in both ribosome biogenesis and recycling.

Initiation factor 2 (IF2) guides the ribosome to the elongation phase of protein synthesis. Here, Basu et al. provide structural insights into how compact IF2-GDP makes way for initiator tRNA accommodation into the peptidyl (P) site of the ribosome.

Ribosome biogenesis is tightly coordinated with cell-cycle progression. By characterizing the SUMO isopeptidases SENP3/SENP5, Doenig et al. identify a long-sought p53-independent impaired ribosome checkpoint that converges on downregulation of CDK6.

Attachment of the ubiquitin-like modifier UFM1 to 60S ribosomes has a critical function in the release and recycling of stalled or terminated ribosomes from the endoplasmic reticulum membrane.

The nascent polypeptide exit tunnel (NPET) is a functional center of the large ribosomal subunit through which the nascent polypeptide chains travel from the peptidyltransferase center (PTC). Here the authors provide structural insight into NPET maturation and how it is linked to other aspects of ribosome biogenesis.

Upon transition to stationary phase or upon stress, bacteria limit protein synthesis through small inhibitory proteins that bind the ribosome. Here the authors decipher the interaction mode of the bacterial ribosome silencing factor (RsfS) at atomic details to provide an in depth view of how it shutdowns ribosomes.

Protein phosphorylation has various regulatory functions. Here, the authors map 241 phosphorylation hotspot regions across 40 eukaryotic species, showing that they are enriched at interfaces and near catalytic residues, and enable the discovery of functionally important phospho-sites.

Otu2-driven deubiquitylation of ribosomal protein eS7 impacts translational efficiency. Here, the authors provide the molecular basis for recognition of monoubiquitinated eS7 on 40S and give mechanistic insights into Otu2’s role in translation reset.

Tsr1 is an essential ribosome biogenesis factor that has known similarity to GTPases. Here, the authors report the Tsr1 crystal structure and show that it is similar to GTPases but that active site residues are not conserved; modelling of the structure into the pre-40S maps allows inferences on ribosomal maturation to be drawn.

Acl4 is a dedicated assembly chaperone for ribosomal protein RpL4 that recognizes RpL4 in the cytoplasm to facilitate its nuclear import. Here the authors reveal the mechanism whereby Acl4 recognizes RpL4 and functions to protect it from Tom1-mediated degradation until RpL4 incorporation into the maturing 60S pre-ribosomal subunit.

The ribosome of bacteria and other unicellular pathogens is a common target for antibiotic drugs. Here the authors determine a structure of the human ribosome bound to the translation inhibitor cycloheximide, and provide evidence that targeting the ribosome is a promising avenue for cancer therapy.

Protein S1, a subunit of the Qß phage RNA-directed RNA polymerase, was thought to only initiate copying of the phage RNA plus strand. Here, the authors show that S1 stimulates replication of any cognate template by promoting release of the newly synthesized product strand.

Membrane proteins are inserted co-transnationally through the association between ribosome, the signal recognition particle and its receptor, and the membrane-bound translocon. Here the authors present a cryo-EM reconstruction of this quaternary complex in the activated state and propose a model for signal sequence transfer to the translocon.

While the cytosolic translation machinery is well characterized, the mitochondrial translation system remains largely elusive. Using cryo-electron tomography, Pfeffer et al. describe the ordered organization of mitochondrial polysomes in which each ribosome is tethered to the inner membrane by two defined contacts on the large subunit in situ.

RPL3L is a paralog of the ribosomal protein RPL3 and specifically expressed in heart and skeletal muscle. Here, the authors show that RPL3L-containing ribosomes regulate translation elongation dynamics especially for the transcripts related to cardiac muscle contraction.

The narrow exit tunnel of the ribosome is important for cotranslational protein folding. Here, authors show that their rationally designed and engineered exit tunnel protein loops modulate the free energy of nascent chain dynamics and folding.

Here the authors find that nascent chains enriched in acidic amino acids destabilize the translating ribosome, eventually leading to stochastic premature termination in eukaryotes as in bacteria. Such risk of premature termination influences the amino acid distribution in the proteomes.

Alternative rescue factor B (ArfB) is an enzyme that releases peptides from stalled ribosomes to allow ribosome recycling. Here the authors carry-out cryo-EM analyses of 70S ribosomes complexed with ArfB on either a short or longer mRNA to reveal distinct modes of ArfB function.

The guided entry of tail-anchored proteins (GET) pathway assists in the delivery of such proteins to the ER. Here, the authors reveal that the pathway components Get4/5 probe a region near the ribosomal exit tunnel. Upon emergence of a client protein, Get4/5 recruits Sgt2 and initiates the targeting phase of the pathway.

During nutrient stress, ribosomal protein abundance is regulated primarily by translational and non-autophagic degradative mechanisms, but ribosome density per cell is largely maintained by reductions in cell volume and rates of cell division.

eIF5A is critical for protein synthesis but has not yet been associated with congenital human disease. Here, the authors show that EIF5A variants cause a Mendelian disorder via reduced eIF5A-ribosome interactions and this phenotype is partially corrected by spermidine supplementation in yeast and zebrafish.

Nop9 is a conserved small ribosomal subunit biogenesis factor. Here, Zhang et al. show that Nop9, in complex with RNA, adopts a C-shaped fold formed from 11 Pumillo repeats and propose that Nop9 inhibits premature cleavage of 20S pre-rRNA by inhibiting the Nob1 nuclease.

The structure of the human ribosome at high resolution has been solved; by combining single-particle cryo-EM and atomic model building, local resolution of 2.9 Å was achieved within the most stable areas of the structure.

Cryo-EM studies of the 60S ribosomal subunit reconstituted with biogenesis factor Arx1 and Rei1 and Jji1 suggest that, in addition to its role during pre-60S nuclear export, Arx1 shields the polypeptide tunnel-exit region and inhibits the premature association of nascent chain–processing factors, whereas Rei1 and Jjj1, which have been implicated in Arx1 recycling, may function in Arx1 release from the tunnel exit.

The authors demonstrate a 3-tier mass spectrometry approach, including bottom-up and top-down proteomics, as well as native mass spectrometry to provide a detailed description of proteoforms, protein processing and post-translational modifications present within ribosomes from bacteria, plant, and human.

Lassard et al. demonstrate a relationship between cellular senescence and perturbed ribosome biogenesis and find that the ribosomal protein S14 is an inhibitor of CDK4, inducing an Rb-dependent cell cycle arrest.

Ribosomes tend to stall during the translation of consecutive proline residues, which can be rescued by the co-translational factor EF-P. Here the authors identify a structural element of tRNA^Proresponsible for specific recognition by EF-P and stimulation of Pro-Pro peptide bond formation.

Under conditions of nutrient limitation, bacterial ribosomes undergo dimerization, forming a 100S complex that is translationally inactive. Here the authors present the structural basis for formation of the 100S complexes in Gram-positive bacteria, shedding light on the mechanism of translation suppression by the ribosome-silencing factors.

The synthesis of ribosomes requires the orderly assembly of many proteins and large RNA molecules, a process that involves several assembly factors. Here the authors show that dedicated chaperones capture the N termini of specific nascent ribosomal proteins to promote folding and assembly into maturing ribosomes.

The nucleolus is a specialized functional domain of the nucleus where ribosome biogenesis is initiated and also implicated in a p53-dependent anti-tumor surveillance. Here the authors use a quantitative imaging approach to detail the role of each ribosomal protein on the structural integrity of the nucleolus and p53 homeostasis.

Excision of internal transcribed spacer 2 (ITS2) within eukaryotic pre-ribosomal RNA is essential for ribosome function. Here, the authors reconstitute the entire cycle of ITS2 processing in vitro using purified components, providing insights into the cleavage process and demonstrating that 26S pre-rRNA processing necessarily precedes 7S pre-rRNA processing.

Ribosome biogenesis involves the hierarchical assembly of several proteins and RNA components. Here the authors describe a mechanism for ribosomal protein S3 incorporation into 40S ribosomal subunits that involves S3 dimerization and stepwise incorporation of two distinct S3 interaction domains coupled to release of ribosomal maturation factors.

Ribosomal proteins are transported to the nucleus with the help of importins, from which they are released prior to incorporation into the nascent ribosome. Here the authors report the NMR structure of the ribosomal protein eS26 in complex with the escortin Tsr2 and shed light on the mechanism of eS26 release from importin.