Although the mechanism of protein splicing is well-determined, the biological functions of post-translational splicing reactions have remained unclear (Vila-Perelló and Muir, 2010). Auto-catalytic protein splicing is a phenomenon that can be found in all three domains of life: archaea, eubacteria and eukaryotes (Bürglin, 2008b).
In archaea has to date been identified many inteins, in bacteria, inteins and three types of bacterial intein-like domains (BIL) can be found, and eukaryotes are proven to contain inteins, Vint and Hog domains unique to them, and even BIL type A domains (Bürglin, 2008; Dassa et al., 2004). The Hogs, Vints and inteins are known to have evolved in parallel in eukaryotes (Bürglin, 2008).
In addition to to their ability to self-excise and ligate, many inteins are also reported to contain an endonuclease domain, separate from and non-participating in protein splicing activity. Of all the domains in the HINT superfamily, only inteins are found in all three domains of life. (Pietrokovski, Shmuel, 2001) Originally, Inteins were assumed to be exclusively selfish parasitic genetic elements, but since then, evidence of them possessing biological functions has emerged (Novikova et al., 2016).
The proteins, in which inteins have been found, have many different functions, such as metabolic enzymes, DNA and RNA polymerases, proteases, ribonucleotide reductases, and even vacuolar-type ATPase, but enzymes needed in DNA replication and repair have been detected to be most represented (Liu, 2000).
According to study results, inteins are found significantly concentrated in proteins that are present in the DNA replication fork, especially in ATPase domains. This discovery applies even on nonorthologous proteins between bacteria and archaea, which is unusual, when taken in consideration that bacterial and archaeal replication machinery are only very distantly related to each other. (Novikova et al., 2016)
At least in the case of Synechocystis sp. PCC6803, split inteins and splicing in trans have been reported to be an essential part in providing the organism with a functional polymerase α subunit, even though the gene in question is dispersed in the genome (Hong Wu et al., 1998). A possibility exists, that Inteins or their subpopulations are located in functionally crucial proteins and are beneficial to the host (Novikova et al., 2016).
Therefore, to some extent can be presumed, that trans-splicing of the organism’s DNA also occurs naturally, and it’s possible that split inteins might have similar functions in other species. (Paulus, 2000)
HINT domains have very diverse roles in biological functions, but research has shown that they have an important part in the correct maturation of Hedgehog proteins (Porter, Jeffery A. et al., 1996). In turn, Hedgehog proteins are essential in Hedgehog signaling pathway, which is a fundamental part of development of eukaryotes, such as effect on segment polarity (Bürglin, 2008).
The function of BIL domains is speculated to be involved with generating post-translational protein variability, particularly in proteins bound for secretion (Dassa et al., 2004). Additional role has been suggested for predatory bacteria with BIL type C domains, which are proposed to be utilized in identifying prey cells (Dori-Bachash et al., 2009).