The Eukaryotic Ribosome: Current Status and Challenges

Abstract

Despite having been identified first, their greater degree of complexity has resulted in our understanding of eukaryotic ribosomes lagging behind that of their bacterial and archaeal counterparts. A much more complicated biogenesis program results in ribosomes that are structurally, biochemically, and functionally more complex. However, recent advances in molecular genetics and structural biology are helping to reveal the intricacies of the eukaryotic ribosome and to address many longstanding questions regarding its many roles in the regulation of gene expression.Since its initial discovery using differential ultracentrifugation of rat liver homogenates (reviewed in Ref. 1), the ribosome has remained a foundational platform upon which our understanding of the relationship between structure and function at the molecular level has been built. There is a rich history of biochemistry and genetics of eukaryotic ribosomes, including the discovery in the 1950s that they 32 are the site of protein synthesis, the elucidation of the function of the nucleolus, and even the discovery of the first eukaryotic RNA polymerase (reviewed in Ref. 2). Whereas early studies using mammalian ribosomes defined the "integral requirements" for protein synthesis, a switch to bacterial ribosomes in the 1960s facilitated the identification of the "minimal requirements" for the translational machinery, giving rise to a "golden age" of translation. In particular, the greater degree of structural and functional complexity makes eukaryotic ribosomes more challenging to work with than their bacterial and archaeal counterparts. For example, whereas bacterial translation initiation requires only a small set of trans-acting factors and is facilitated by the ShineDalgarno sequence, this process in eukaryotes requires a multifactorial complex of trans-acting factors that is almost as massive as the ribosome itself (reviewed in Ref. 3). Here, some of the current topics and challenges in the study of the eukaryotic ribosome are reviewed.

Bypass of the pre-60S ribosomal quality control as a pathway to oncogenesis

“…Mammalian ribosomal proteins have also been shown to have functions independent of protein translation, however [reviewed in (42,43)]. In particular, RPL10/uL16 has been linked to regulation of the oncogenic transcription factor JUN (44) and the V-Yes-1 Yamaguchi sarcoma viral oncogene homolog 1 (45).…”

Ribosome Biogenesis in the YeastSaccharomyces cerevisiae

“…Or misassembly could create malfunctioning ribosomal subunits whose presence could interfere with remaining functional subunits. Even single missense mutations in rproteins or rRNA can alter the structure and dynamics of otherwise intact ribosomal subunits, leading to decreased fidelity of protein synthesis (Dinman 2009). Thus, mechanisms for proofreading assembly of preribosomes and for destruction of misassembled preribosomes are of crucial importance.…”

Eukaryote-specific extensions in ribosomal proteins of the small subunit: Structure and function

“…1,2 Eukaryotic 80S ribosomes (composed of 60S and 40S subunits) have evolved to be much larger in size with more proteins and ribosomal RNA (rRNA) than their archeal, or bacterial counterparts, (70S ribosomes composed of 50S and 30S subunits). [3][4][5][6] Recent X-ray crystal structures of the yeast 80S ribosome at 3.0 A resolution permitted detailed analysis of the structural organization of the eukaryotic ribosome. 5,6 It became evident that bacterial and eukaryotic ribosomes evolved from a common structural (RNP) core with the majority of changes occurring on the outer shell of the ribosome.…”