Abstract
Inteins are mobile genetic elements that apply standard enzymatic strategies to excise themselves post-translationally from the precursor protein via protein splicing. Since their discovery in the 1990s, recent advances in intein technology allow for them to be implemented as a modern biotechnological contrivance. Radical improvement in the structure and catalytic framework of cis- and trans-splicing inteins devised the development of engineered inteins that contribute to various efficient downstream techniques. Previous literature indicates that implementation of intein-mediated splicing has been extended to in vivo systems. Besides, the homing endonuclease domain also acts as a versatile biotechnological tool involving genetic manipulation and control of monogenic diseases. This review orients the understanding of inteins by sequentially studying the distribution and evolution pattern of intein, thereby highlighting a role in genetic mobility. Further, we include an in-depth summary of specific applications branching from protein purification using self-cleaving tags to protein modification, post-translational processing and labelling, followed by the development of intein-based biosensors. These engineered inteins offer a disruptive approach towards research avenues like biomaterial construction, metabolic engineering and synthetic biology. Therefore, this linear perspective allows for a more comprehensive understanding of intein function and its diverse applications.
Highlights
Splicing mechanism can be broadly categorized as RNA splicing and protein splicing, two mechanisms responsible for the flow of information from a gene to its protein product to yield a functional protein whose sequence is strictly noncolinear with the gene
This extensive phylogenetic distribution pattern of inteins contemplates their nature as a mobile genetic element
homing endonuclease domain (HED) associate with inteins? How effortlessly does intein transfer occur among related organisms? Inteins seem to be biased, but not limited to host proteins involved in DNA repair and replication, possibly since it may shuttle intein genes across organisms, help in intein homing and make inteins less harmful to host cell by limiting intein endonuclease production during times of active DNA repair
Summary
Splicing mechanism can be broadly categorized as RNA splicing and protein splicing, two mechanisms responsible for the flow of information from a gene to its protein product to yield a functional protein whose sequence is strictly noncolinear with the gene. Inteins are biased towards invading regulatory proteins that are responsible for DNA metabolisms (polymerases, topoisomerases, helicases, ribonucleotide reductases) and essential housekeeping genes, including essential proteases, metabolic enzymes, RNA processing proteins and energy supplying vital proteins Their insertion site coincides with the conserved domains, responsible for host protein function like catalytic or ligand binding sites, enzyme active site, DNA binding sites etc. This site-specific behaviour of intein insertion may be due to the functionality of housekeeping genes, including essential proteases, metabolic enzymes, RNA processing proteins and energy supplying vital proteins Their insertion site coincides with the conserved domains, Mreiscrpooorngasniibsmles f2o02r0h, 8o, s2t00p4rotein function like catalytic or ligand binding sites, enzyme active site, D5 oNf 3A0 binding sites etc. Insertion at these critical sites ensures the survivability of inteins, making itthsehmomleisnsg pernodnoenutocledaesletdioonms.aiTnh[i1s0s].itTe-hsepeacmifoicunbteohfaviniofourrmoaftiionntecionnicnesiveretdiornegmaradyinbgethdeuegetnoomthe ofurgnacntiioznaatiloitny aonfditesxphroemssinogn oefnidnotneiuncsleiansethedolamstaitnwo[1d0]e.caTdhees hamasoluendt toofthienfuonrmdeartsiotanndcionngceaisvetod hreogwarmdionbgiltehgeegneentiocmeeleomregnantsizaarteionnotasnodleelxyppraersasisoitnicosfeiqnuteinncseisn, btuhet alalssot thwavoedaecdaydneasmhiacsrloelde itno the euvnodluertsiotannodfinspgeacsietso. how mobile genetic elements are not solely parasitic sequences, and have a dynamic role in the evolution of species
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