Mitochondrially encoded tRNA leucine 1 (UUA/G) also known as MT-TL1 is a

transfer RNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

which in humans is encoded by the

mitochondrial A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

''MT-TL1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Structure

The ''MT-TL1'' gene is located on the p arm of the

mitochondrial DNA Mitochondrial DNA (mtDNA and mDNA) is the DNA located in the mitochondrion, mitochondria organelles in a eukaryotic cell that converts chemical energy from food into adenosine triphosphate (ATP). Mitochondrial DNA is a small portion of the D ...

at position 12 and it spans 75 base pairs. The structure of a

tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed

clover Clovers, also called trefoils, are plants of the genus ''Trifolium'' (), consisting of about 300 species of flowering plants in the legume family Fabaceae originating in Europe. The genus has a cosmopolitan distribution with the highest diversit ...

Function

MT-TL1 is a small 75 nucleotide

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

(human mitochondrial map position 3230–3304) that transfers the amino acid

leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-Car ...

to a growing

polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

chain at the

ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

site of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

synthesis during

translation Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...

. Also, some studies showed that the ''MT-TL1'' gene pathogenic variants could be attributed to the alterations of mTERF binding efficiency.

Clinical significance

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

Mutations in ''MT-TL1'' can result in multiple mitochondrial deficiencies and associated disorders. It is associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes ( MELAS). MELAS is a rare mitochondrial disorder known to affect many parts of the body, especially the

nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...

and the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

. Symptoms of MELAS include recurrent severe

headaches A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Head ...

, muscle weakness (

myopathy In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. ''Myopathy'' means muscle disease ( Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meaning implies that the primary defec ...

hearing loss Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spo ...

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

-like episodes with a loss of

consciousness Consciousness, at its simplest, is awareness of a state or object, either internal to oneself or in one's external environment. However, its nature has led to millennia of analyses, explanations, and debate among philosophers, scientists, an ...

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

, and other problems affecting the

. A common mutation is A3243G. This mutation has been theorized to be associated with several other mitochondrial diseases, including diabetes mellitus and deafness. Diabetes mellitus and deafness is characterized by

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

combined with

, particularly of high pitches. Additional symptoms include

muscle weakness Muscle weakness is a lack of muscle strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, includ ...

(

) and various problems with a patient's eyes, heart, or kidneys. Other rare point variants on ''MT-TL1'' gene were also described: m.3271 T > C, m.3291 T > C, m.3303 C > T, m.3256 C > T, and m.3260 A>G.

Complex I deficiency

''MT-TP'' mutations may result in complex I deficiency of the mitochondrial respiratory chain, which may cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the

, the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

, and the muscles used for movement (

skeletal muscles Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

). These signs and symptoms can appear at any time from birth to adulthood. Phenotypes of the condition include

encephalopathy Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

dystonia Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po ...

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but it is a potential manifestation of many different dis ...

myalgia Myalgia or muscle pain is a painful sensation evolving from muscle tissue. It is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likely cause is viral infection, espec ...

exercise intolerance Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe pos ...

, and more. A 3302A>G mutation has been found in a patient with the deficiency.

References

External links

GeneReviews/NCBI/NIH/UW entry on Mitochondrial DNA-Associated Leigh Syndrome and NARP

GeneReviews/NCBI/NIH/UW entry on MELAS