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Conspicuous tRNA Lookalikes Riddle the Human Genome

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Transfer tRNAs are part of the processes taking part in the cells that create proteins needed to keep a cell running smoothly.


In a new study, it has been suggested that it is likely that the number of human genomic loci which could be coding for tRNAs are nearly double of what is known today. The newly identified loci show resemblance to the sequences of mitochondrial tRNAs which suggests that there are unexpected new links between the human nuclear and mitochondrial genomes which are not currently understood by scientists till now. The tRNAs are an integral part of the process of translation of a messenger mRNA into a sequence of amino acids. TRNAs which are the non-coding RNA molecules can be found in all three kingdoms of life i.e., in archaea, bacteria and eukaryotes.

At the DNA level, a triplet of consecutive nucleotides known as the “codon” is used to encode an amino acid. There are 61 distinct codons which encodes the 20 standard human amino acids. When the translation occurs, each of the codons contained in the coding region of the mRNA at hand is recognized by its matching tRNA and the corresponding amino acid added to the nascent amino acid sequence.

We have known for many years now that each of these 61 tRNAs has multiple copies spread throughout the genome which is found in the human nucleus. The presence of multiple genomic loci from which the same molecule can be made is a process of genomic organization. By processing these loci in parallel ensures that adequate amounts of each tRNA can be generated quickly enough to meet the high demand that the amino acid translation process imposes on the cell.

In addition to the 61 tRNAs that are found in the human nuclear genome, 22 more tRNAs are encoded in the genome of the cellular organelle known as the mitochondrion. originally a bacterium itself, the mitochondrion, uses these 22 tRNAs to make proteins out of the just-over-a-dozen mRNAs that are encoded in its genome.

Through recent researches, it has been discovered now that the tRNAs can have other roles too, which go beyond their involvement in protein synthesis.  It is seen that tRNAs has the ability to affect the physiology of a cell. In fact, they can modulate the abundance of important molecules, etc. Such interesting findings have revived interest in looking at tRNAs under a different light.

A team led by Isidore Rigoutsos, Director of the Computational Medicine Center at Thomas Jefferson University (TJU), set out to find how many tRNAs are actually encoded by the human genome and could be potentially involved in amino acid translation and other processes. Rigoutsos remarked what their study revealed surprised them.

The report on their findings was just published in the journal Frontiers in Genetics. For the study, the team searched the 3 billion base pairs of the human genome for DNA sequences that resembled the 530 known nuclear and mitochondrial tRNAs.  A very stringent criteria was used in their searches, however they found 454 “lookalike” loci. It means that sequences look like tRNA, but are not yet been experimentally confirmed as such. Also, it was discovered that 81% of these tRNA-lookalikes had not been reported previously. The researchers were surprised to find that most of these new loci resembled some of the 22 mitochondrial tRNAs. It was also interesting to note that the discovered tRNA lookalikes did not seem to be spread uniformly across the 24 chromosomes. What was discovered was that they have penetrated preferentially some chromosomes and have avoided others.

The team also made the discovery that in the chromosomes where the tRNA-lookalikes are found, their locations are not accidental.  It seems that the lookalikes are positioned in close proximity to known nuclear tRNAs, which gives rise to the question if the tRNA-lookalikes are transcribed, just like the known tRNAs. The team found after thoroughly examining public repositories that there is evidence of transcription for more than 20% of the discovered tRNA-lookalikes. Rigoutsos remarked that though it sounds exciting, it is unclear if these molecules participate in translation as tRNAs, or if they have entirely different roles.