Transfer RNAs (tRNAs) are ancient workhorse molecules and part of the cellular process that creates the proteins, critical building blocks of life that keep a cell running smoothly.
A new discovery suggests that the number of human genomic loci that might be coding for tRNAs is nearly double what is currently known. Most of the newly identified loci resemble the sequences of mitochondrial tRNAs suggesting unexpected new links between the human nuclear and mitochondrial genomes, links that are not currently understood.
Transfer RNAs (tRNAs) represent an integral component of the translation of a messenger RNA (mRNA) into an amino acid sequence. TRNAs are non-coding RNA molecules and 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. Frequently, a given amino acid can be encoded by more than one codon: in fact, there are 61 distinct codons encoding the 20 standard human amino acids. During translation, 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.
It has been known for many years that each of these 61 tRNAs has multiple copies spread throughout the genome that is found in the human nucleus. The presence of multiple genomic loci from which the same molecule can be made is a fairly standard trick of genomic organization: processing these loci in parallel can ensure 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: the mitochondrion, originally a bacterium itself, uses these 22 tRNAs to make proteins out of the just-over-a-dozen mRNAs that are encoded in its genome.
Recent research efforts have shown that tRNAs can have other roles, which go beyond their involvement in protein synthesis. For example, tRNAs can affect the physiology of a cell, they can modulate the abundance of important molecules, etc. These and other unexpected findings have revived interest in looking at tRNAs, this time under a different prism. But, how many tRNAs are actually encoded by the human genome and could be potentially involved in amino acid translation and other processes?
A team led by Isidore Rigoutsos, Director of the Computational Medicine Center at Thomas Jefferson University (TJU), set out to tackle this question and they have reported their findings in a study that was just published in the journal Frontiers in Genetics. "What we found, frankly, surprised us," said Rigoutsos.
The team searched the 3 billion base pairs of the human genome for DNA sequences that resembled the 530 known nuclear and mitochondrial tRNAs. Even though they used very stringent criteria in their searches, they found 454 "lookalike" loci, i.e., sequences that look like tRNA, but haven't yet been experimentally confirmed as such. The researchers found nearly as many as the known ones with which they started: 81% of these tRNA-lookalikes had not been reported previously. Rather unexpectedly, the team found that most of these new loci resembled some of the 22 mitochondrial tRNAs.
Interestingly, the discovered tRNA lookalikes are not spread uniformly across the 24 chromosomes. Instead, they have penetrated preferentially some chromosomes and have avoided others. For example, chromosomes 1, 2, 7, 8 and 9 claim the lion's share of the discovered tRNA-lookalikes. On the other hand, chromosome 18 contains no lookalikes. Also, some of the codons are particularly over-represented among the lookalikes whereas other codons are absent.
The surprises did not stop there. The team also discovered that in the chromosomes where the tRNA-lookalikes are found their locations are not accidental either. Instead, the lookalikes are positioned in close proximity to known nuclear tRNAs. This of course begs the question whether the tRNA-lookalikes are transcribed, just like the known tRNAs. By examining public repositories, the team found evidence of transcription for more than 20% of the discovered tRNA-lookalikes: the transcriptional profiles appear to depend on cell type, which suggests that more of the look-alikes will be found to be transcribed as data from more cell types become available. On several occasions, the public data revealed evidence for molecules whose endpoints matched exactly the endpoints of the tRNA-lookalikes discovered by the team. "This is certainly exciting, but it is currently unclear whether these molecules participate in translation as tRNAs, or have entirely different roles," said Rigoutsos.
The authors report no conflicts of interest.
For more information, contact Edyta Zielinska, 215-955-5291, firstname.lastname@example.org.
Thomas Jefferson University (TJU), the largest freestanding academic medical center in Philadelphia, is nationally renowned for medical and health sciences education and innovative research. Thomas Jefferson University includes the Sidney Kimmel Medical College (SKMC), one of the largest private medical schools in the country and ranked among the nation's best medical schools by U.S. News & World Report, the Graduate School of Biomedical Sciences and the Jefferson Schools of Nursing, Pharmacy, Health Professions, and Population Health. Jefferson University Physicians is TJU's multi-specialty physician practice consisting of the full-time faculty of SKMC. Thomas Jefferson University partners with its clinical affiliate, Thomas Jefferson University Hospitals.
A.G. Telonis et al., "Nuclear and mitochondrial tRNA-lookalikes in the human genome," Frontiers in Genetics, doi: 10.3389/fgene.2014.00344, 2014.
Edyta Zielinska | Eurek Alert!
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences