Interaction of rRNA with mRNA and tRNA in Translating Mammalian Ribosome: Functional Implications in Health and Disease

Abstract

RNA-RNA interaction slowly emerges as a critical component for the smooth functioning of gene expression processes, in particular in translation where the central actor is an RNA powered molecular machine. Overall, ribosome dynamic results from sequential interactions between three main RNA species: ribosomal, transfer and messenger RNA (rRNA, tRNA and mRNA). In recent decades, special attention has been paid to the physical principles governing codon-anticodon pairing, whereas individual RNA positioning mostly relies on ribosomal RNA framework. Here, we provide a brief overview on the actual knowledge of RNA infrastructure throughout the process of translation in mammalian cells: where and how do these physical contacts occur? What are their potential roles and functions? Are they involved in disease development? What will be the main challenges ahead?

Keywords: RNA modification; RNA-RNA interaction; X-linked dyskeratosis congenital; hepatitis C virus (HCV); mammalian ribosome; messenger RNA (mRNA); ribosomal RNA (rRNA); transfer RNA (tRNA).

Figure 1

Schematic representation of the structural hallmarks and functional sites of the two mature ribosomal subunits (interface subunit view). The 40S subunit is organized in different structural regions: the body, the head, the shoulder, the beak, and the left and right feet. The 60S subunit structural landmarks are the central protuberance, the L1 and P stalks and the sarcin–ricin loop. Messenger RNA (mRNA) enters the mRNA channel through the mRNA entry site and exits through the mRNA exit site. The mRNA codon is read by its cognate transfer RNA (tRNA) in the decoding center (DC). The peptide bond formation occurs at peptidyl transferase center (PTC). The incoming aminoacyl tRNA enters in the A site, the P site holds the peptidyl tRNA, deacetylated tRNA binds the E site before it dissociates from the ribosome.

Figure 2

Illustration of secondary structure of tRNA. This cloverleaf shaped structure is due to four base-paired stems, three of them terminating with non-base-paired loops: D loop, anticodon loop, and TψC loop. Nucleotide modifications found in tRNA^Tyr, one of the most modified tRNA, are annotated in red. Short names of individual modification are given according to the RNA modification databases (e.g., Modomics). Ψ, pseudouridine; D, dihydrouridine; m¹A, N¹-methyladenosine; m¹G, N¹-methylguanosine; m¹ψ, N¹-methylpseudouridine; m²G, N²-methylguanosine, m²₂G, N²,N²-dimethylguanosine; m⁷G, N⁷-methylguanosine; m⁵C, N⁵-methylcytidine; m⁵U, N⁵-methyluridine; Gal-Q, galactosyl-queuosine; acp³U, 3-(3-amino-3-carboxypropyl)uridine.