Bonds from the past: A journey through the history of protein synthesis
Scientists provide evolutionary insights into protein synthesis using primordial transfer RNA and ribosomes

Date:
April 21, 2022
Source:
Tokyo University of Science
Summary:
The process of 'translation' in protein synthesis involves formation
of a peptide bond between two amino acids that are attached to
two distinct transfer RNAs (tRNAs). For long, scientists have been
puzzled as to how these tRNAs evolutionarily lie so close to each
other on the ribosome. In a new study, researchers explain how
tRNA-like components act as scaffolds for peptide bond formation
between amino acid-bound 'RNA minihelices,' which are half tRNA-like
molecules.



FULL STORY ==========================================================================
The process of "translation" in protein synthesis involves formation
of a peptide bond between two amino acids that are attached to two
distinct transfer RNAs (tRNAs). For long, scientists have been puzzled
as to how these tRNAs evolutionarily lie so close to each other on the ribosome. In a new study, researchers explain how tRNA-like components
act as scaffolds for peptide bond formation between amino acid-bound
"RNA minihelices," which are half tRNA-like molecules.


==========================================================================
The genetic information stored in DNA is "decoded" to form proteins via
the process of translation. This involves the formation of peptide bonds between amino acids bound to transfer RNA (tRNA) molecules that glide
over the ribosome in very close proximity to each other, and elongate
the peptide chain, which later undergoes conformational change, forming
a protein. In contrast to the codon-dependent aminoacyl-tRNA recognition
in the small ribosomal subunit, the peptide bond formation in question
occurs at the peptidyl transferase center (PTC) of the large ribosomal
subunit, in a non-amino acid specific manner. This non-specificity
indicates that the large subunit evolved before the small subunit,
which has more specific interactions with mRNA and tRNA.

Although the evolutionary process of PTC formation has been thoroughly documented, little is known about how ribosomes developed into
functioning entities and became an essential component of protein
synthesis. Scientists have long been perplexed by the fact that tRNAs
require the help of a "scaffold" in order to create a peptide bond,
which orients them for interaction via 3'-CCA sequences on their acceptor
arms. What that scaffold is, and how it operates, would be intriguing
to learn about.

A team of scientists at Tokyo University of Science, led by Prof. Koji
Tamura, decided to solve this mystery using a perspective of continuity
in biological evolution. Their study, which was published online on 12
April 2022 in Volume 12, Issue 4 of the journal Life, sheds light on
the evolutionary aspect of protein translation. Their results represent important evidence to demonstrate the hypothesis about the origin and
evolution of the PTC, which has changed the way we look at the modern-day ribosomes and tRNA.

The idea sprang to life after taking a close look at the crystal
structure of the 70S ribosome-tRNA complex from Thermus thermophilus,
a bacterium often used in the study of genetics. The peptidyl (P-)
and aminoacyl (A-) sites of the tRNAs here aligned to bring the CCA
termini in close proximity, like a rugby player's index fingers in the "Goromaru pose." "There was a certain entity that served as a scaffold for maintaining this proximity, and it most likely stemmed from the primordial PTC," says Prof. Tamura. Since an evolutionary aspect was likely, the
team chose to utilize primordial tRNA or "RNA minihelix" for their study.

They first attempted a peptide bond formation between two alanine-specific minihelices in the presence of a ribosomal RNA segment. The peptide bond
was formed using the ribosomal segment, P1c2, as an RNA scaffold which
was just 70 nucleotides long! Next, they added a terminal amino acid
segment (with the sequence UGGU) to the P1c2 (P1c2UGGU). According to
mass spectrometry results, this increased the peptide bond formation
ability by 4.2 times that of the original! The peptide bond formation
between two alanine residues was supported by a scaffold of dimerized
P1c2UGGU. The UGGU sequence of the scaffold interacted with the
corresponding 3'-terminal ACCA of the minihelix and brought the two
amino acids near enough to create a peptide bond. Nobel laureate Dr.

Ada Yonath and her group recently showed that similar, conserved PTC
regions could catalyze peptide bond formation with artificial analog
molecules, but Prof. Tamura's group showed that an aminoacylated RNA
could also be a substrate.

The findings definitely imply a possibility that minihelices bind to
the primordial PTC. So, what do the results suggest about the evolution
of ribosomes? "Functional interactions between the CCA of tRNA and
PTC could have been 'revised' in the process of evolution. Although
current ribosomes do not have a contiguous sequence like UGGU, their interactions are 'conceptually' similar to the effects seen in our
study. It is plausible that minihelices eventually evolved into tRNA
using, for example, kissing-loop interactions between two minihelix-like
RNA molecules," Prof. Tamura explains. "These minihelix-like molecules,
which form a part of the scaffold for peptide bond formation, may have
not only contributed to the evolution of what is currently the PTC,
but also formed tRNA molecules," he adds.

The future applications of this research -- which has opened up exciting avenues in evolutionary RNA biology -- are manifold. Faced with a
metabolic paradox (that the components of DNA and RNA are generated
from amino acids), it is conceivable to investigate the notion of
"peptide nucleic acids" as genetic material precursors. The results are fascinating, and they will help scientists to decode molecular phenomena
that have eluded them for years.


========================================================================== Story Source: Materials provided by Tokyo_University_of_Science. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Mai Kawabata, Kentaro Kawashima, Hiromi Mutsuro-Aoki, Tadashi Ando,
Takuya Umehara, Koji Tamura. Peptide Bond Formation between
Aminoacyl- Minihelices by a Scaffold Derived from the Peptidyl
Transferase Center.

Life, 2022; 12 (4): 573 DOI: 10.3390/life12040573 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220421100146.htm

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