About tRNA

Transfer RNAs (tRNAs) are small RNA molecules containing 75 to 95 nucleotides.

Cells contain many different tRNA molecules. Most of the tRNAs function as carriers
of amino acids and participate in protein synthesis. However, tRNAs also take part in
reactions not related to ribosome-dependent translation. The first nucleic acid to be
completely sequenced was the tRNA that binds the amino acid alanine (tRNAAla).
This pioneering work was performed by Holley and co-workers long before the
invention of today's rapid sequencing techniques. For his work, Holley received the
1968 Nobel Prize in Physiology or Medicine.
The obtained sequence information showed that tRNAAla (tRNA with an anticodon
corrsponding to the amino acid alanine see the genetic code) contained a series of
inverted sequences that allows folding of the linear RNA molecule in a cloverleaf
configuration (secondary structure). It was subsequently shown that the cloverleaf
structure was compatible with the sequence of almost all tRNAs. In the cloverleaf
model, the inverted sequences form four double-helical segments. The two ends of
the molecule form the amino acid arm or acceptor stem. A single strand sequence CCA - protrudes from the 3-end of the molecule. The terminal A is coupled to the
amino acid during amino acid activation. The next arm, moving clockwise, is the
TPsiC arm. This arm got its name from the occurrence of the sequence TPsiC in
almost all tRNAs (Psi, pseudouridine, is a modified U). In eukaryotic initiator tRNAs,
TPsiC is substituted for by AUC or APsiC. The next arm is the variable arm which
may contain between 4 and 21 nucleotides. Adjacent to the variable arm is the
anticodon arm with the three nucleotide anticodon which pairs with the codon
during translation. The last arm of the tRNA is the DHU-arm named after the
occurrence of dihydrouridine in all tRNAs. In the early 1970s, the three-dimensional
structure of tRNA was determined by X-ray diffraction of tRNA crystals. It was found
that the basic cloverleaf structure proposed by Holley was further folded into an Lshaped structure. In this structure the CCA-end and the anticodon loop are
positioned at opposite ends of the molecules while the DHU and the TPsiC-arms are
folded in along the axis of the molecule.
Immediately after synthesis, the tRNA, like all RNAs, contains the four bases A, G, C
and U. However, mature tRNAs can contain modified bases i.e., bases other than
the normal A,U,G, and C. These modifications are introduced after transcription of
the tRNA. Most modified bases occur at restricted sites in the tRNA. The first base in
the anticodon, the wobble position, often contains modified bases that allow
formation of unusual base pairs with the third base in the mRNA codon.