Homo sapiens-mtDNA~NC 012920-ATP8+ATP6 Overlap

The start codon is the first

codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...

of a

messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the p ...

(mRNA) transcript translated by a

ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...

. The start codon always codes for

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

s and

Archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...

and a N-formylmethionine (fMet) in bacteria,

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

and

plastid The plastid (Greek: πλαστός; plastós: formed, molded – plural plastids) is a membrane-bound organelle found in the Cell (biology), cells of plants, algae, and some other eukaryotic organisms. They are considered to be intracellular endosy ...

s. The most common start codon is AUG (i.e., ATG in the corresponding DNA sequence). The start codon is often preceded by a 5' untranslated region (

5' UTR The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly upstream from the initiation codon. This region is important for the regulation of ...

). In

prokaryotes A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...

this includes the

ribosome binding site A ribosome binding site, or ribosomal binding site (RBS), is a sequence of nucleotides upstream of the start codon of an mRNA transcript that is responsible for the recruitment of a ribosome during the initiation of translation. Mostly, RBS refers t ...

Alternative start codons

Alternative start codons are different from the standard AUG codon and are found in both

(bacteria and archaea) and

eukaryotes Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

. Alternate start codons are still translated as Met when they are at the start of a protein (even if the codon encodes a different amino acid otherwise). This is because a separate

transfer RNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...

(tRNA) is used for initiation.

Eukaryotes

Alternate start codons (non-AUG) are very rare in eukaryotic genomes. However, naturally occurring non-AUG start codons have been reported for some cellular mRNAs. Seven out of the nine possible single-nucleotide substitutions at the AUG start codon of

dihydrofolate reductase Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In ...

are functional as translation start sites in mammalian cells. In addition to the canonical Met-tRNA Met and AUG codon pathway, mammalian cells can initiate translation with

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- ca ...

using a specific leucyl-tRNA that decodes the codon CUG. ''

Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is us ...

'' uses a CAG start codon.

Prokaryotes

Prokaryotes use alternate start codons significantly, mainly GUG and UUG. These alternate start codons and the frequency of their use compared to eukaryotes has been studied and shown to refute the common ancestor theory.

E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

uses 83% AUG (3542/4284), 14% (612) GUG, 3% (103) UUG and one or two others (e.g., an AUU and possibly a CUG). Well-known coding regions that do not have AUG initiation codons are those of ''lacI'' (GUG) and ''lacA'' (UUG) in the ''

lac operon The ''lactose'' operon (''lac'' operon) is an operon required for the transport and metabolism of lactose in ''E. coli'' and many other enteric bacteria. Although glucose is the preferred carbon source for most bacteria, the ''lac'' operon allows ...

. Two more recent studies have independently shown that 17 or more non-AUG start codons may initiate translation in ''E. coli''.

Mitochondria

Mitochondrial genome Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, such as adenosine triphosphate (ATP). Mitochondrial D ...

s use alternate start codons more significantly (AUA and AUG in humans). Many such examples, with codons, systematic range, and citations, are given in the NCBI list of translation tables.

Upstream start codons

These are "alternative" start codons in the sense that they upstream of the regular start codons and thus could be used as alternative start codons. More than half of all human

mRNAs In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the p ...

have at least one AUG codon upstream (uAUG) of their annotated translation initiation starts (TIS) (58% in the current versions of the human

RefSeq The Reference Sequence (RefSeq) database is an open access, annotated and curated collection of publicly available nucleotide sequences ( DNA, RNA) and their protein products. RefSeq was first introduced in 2000. This database is built by National ...

sequence). Their potential use as TISs could result in translation of so-called upstream

Open Reading Frames In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...

(uORFs). uORF translation usually results in the synthesis of short polypeptides, some of which have been shown to be functional, e.g., in ASNSD1, MIEF1,

MKKS McKusick–Kaufman/Bardet–Biedl syndromes putative chaperonin is a protein that in humans is encoded by the ''MKKS'' gene. This gene encodes a protein with sequence similarity to the chaperonin family. The encoded protein may have a role in pro ...

, and SLC35A4. However, it is believed that most translated uORFs only have a mild inhibitory effect on downstream translation because most uORF starts are leaky (i.e. don't initiate translation or because ribosomes terminating after translation of short ORFs are often capable of reinitiating).

Standard genetic code

Engineered start codons

Engineered initiator tRNAs (tRNA^fMet2 with CUA anticodon) have been used to initiate translation at the amber stop codon UAG. This type of engineered tRNA is called a

nonsense suppressor A nonsense suppressor is a factor which can inhibit the effect of the nonsense mutation. Nonsense suppressors can be generally divided into two classes: a) a mutated tRNA which can bind with a termination codon on mRNA; b) a mutation on ribosomes de ...

tRNA because it suppresses the translation stop signal that normally occurs at UAG codons. One study has shown that the amber initiator tRNA does not initiate translation to any measurable degree from genomically-encoded UAG codons, only plasmid-borne reporters with strong upstream Shine-Dalgarno sites.

References

External links

* The Genetic Codes. Compiled by Andrzej (Anjay) Elzanowski and Jim Ostell, National Center for Biotechnology Information (NCBI), Bethesda, Maryland, U

{{GeneticTranslation DNA Molecular genetics