RNA ligase 1 is a enzyme that in humans is encoded by the gene RLIG1 (previously C12orf29). RNA ligase 1 functions as an RNA ligase, and participates in the biological response to reactive oxygen species.

Gene The RLIG1 gene is located on the positive strand at 12q21.32 in humans (p = short arm, q = long arm). It has 7 exons and 6 introns. The gene spans from 88,035,536 to 88,050,160 with 14,645 base pairs. There is only one isoform of the transcript, which is the transcript of this gene itself.

Neighbor genes around human RLIG1 are: C12orf50 (-), RNA5SP364 (+), LOC107984542 (-), LOC100420011 (+), CEP290 (-).

Expression The RLIG1 gene is ubiquitously expressed in 27 tissues. It is expressed a little bit higher in esophagus, skin, brain and bone marrow. It showed increased expression in several tumor cells and tissues such as in colorectal tumor tissue, in ovarian cancer epithelial cells, and in hyperplastic enlarged lobular units epithelial cells.

Protein RLIG1 protein has 325 amino acids. The molecular weight is 37.5 kD, and the isoelectric point is 6.6 pH. It is not a membrane protein, and it stays in the cytosol. For the content of the amino acids, compared with other human proteins, RLIG1 is high in asparagine and histidine, but it is low in alanine. There are no validated domains or motifs. It has a short repetitive structures of "INGNP", but it is not conserved in orthologs. However, there are two highly conserved predicted motifs. They are the protease caspase 3 and 7 cleavage motif, and the mitogen-activated protein kinase (MAPK) docking motif. There are several predicted protein kinase c phosphorylation sites and casein kinase II phosphorylation sites, but they are not conserved in orthologs. 1 MKRLGSVQRK MPCVFVTEVK EEPSSKREHQ PFKVLATETV SHKALDADIY SAIPTEKVDG 61 TCCYVTTYKD QPYLWARLDR KPNKQAEKRF KNFLHSKENP KEFFWNVEED FKPAPECWIP 121 AKETEQINGN PVPDENGHIP GWVPVEKNNK QYCWHSSVVN YEFEIALVLK HHPDDSGLLE 181 ISAVPLSDLL EQTLELIGTN INGNPYGLGS KKHPLHLLIP HGAFQIRNLP SLKHNDLVSW 241 FEDCKEGKIE GIVWHCSDGC LIKVHRHHLG LCWPIPDTYM NSRPVIINMN LNKCDSAFDI 301 KCLFNHFLKI DNQKFVRLKD IIFDV

Protein interaction NCL and LRRK2 was experimentally determined to interacted with RLIG1. NCL physically interacted with RLIG1, and LRRK2 was associated with RLIG1. There are several predicted protein interactions for RLIG1. The interactions with PNN, OTUD68, and ACTR6 were predicted by co-expression.

Homology and evolution Orthologs of RLIG1 protein are found within the mammals, birds, reptiles, amphibians, fishes, and invertebrates. The length and contents of the protein sequence was highly conserved in the selected orthologs (table below). It is important to notice that the RLIG1 protein was only found in mollusks, tunicate, and cephalochordata in invertebrates, but it was not found in insects, arachnids, crustaceans, corals, worms, jellyfishes, sponges within the other groups in invertebrates. RLIG1 protein was not found in bacteria, fungi, and viruses. There is no paralog for RLIG1 protein. The mutation rate of RLIG1 was close to that of fibrinogen alpha chain. The human's RLIG1 protein was more closely related to the sheep's ortholog than to the mouse's ortholog. The invertebrates RLIG1 orthologs were mostly distantly related to the human protein.

Ortholog table +Selected Orthologs Table of RLIG1 ProteinSequence NumberOrtholog GroupGenius and SpeciesTaxonomic GroupCommon NameTime Since Divergence (Estimated MYA)Accession NumberSequence Length (aa)Sequence IdentitySequence Similarity1MammalsHomo sapiensPrimatesHuman0NP_001009894.2325100%100%2MammalsMus musculusRodentiaHouse Mouse90NP_780337.232784%90%3MammalsOvis ariesArtiodactylaSheep96NP_001186723.132591%96%4MammalsPhascolarctos cinereusDiprotodontiaKoala159XP_020849155.132586%92%5MammalsOrnithorhynchus anatinusMonotremataPlatypus177XP_028934667.132678%89%6AvesGallus gallusGalliformesChicken312XP_040518235.132475%86%7AvesCygnus atratusAnseriformesBlack Swan312XP_035407728.132475%86%8AvesCalypte annaApodiformesAnna's Hummingbird312XP_030312194.132475%87%9ReptilesCrocodylus porosusCrocodyliaAustralian Saltwater Crocodile312XP_019400824.132376%88%10ReptilesZootoca viviparaSquamataCommon Lizard312XP_034983157.132571%85%11ReptilesPython bivittatusSquamataBurmese Python312XP_007429130.132370%84%12ReptilesDermochelys coriaceaTestudinesLeatherback Sea Turtle312XP_038257651.132578%90%13AmphibiansBufo bufoAnuraCommon Toad351.8XP_040264560.132463%77%14AmphibiansRhinatrema bivittatumGymnophionaTwo-lined Caecilian351.8XP_029457527.133566%82%15FishesDanio rerioCypriniformesZebrafish435NP_001008606.132560%79%16FishesRhincodon typusOrectolobiformesWhale Shark473XP_020369226.133056%73%17InvertebratesStyela clavaStolidobranchiaAsian Tunicate676XP_039256956.135144%59%18InvertebratesBranchiostoma floridaeAmphioxiformesFlorida Lancelet684XP_035678444.134143%62%19InvertebratesPecten maximusPectinidaKing Scallop797XP_033752428.134744%62%20InvertebratesCrassostrea gigasOstreidaPacific Oyster797XP_034327602.135741%59%

In research

In bone In sheep (Ovis aries) bone, RLIG1 protein has a high expression in mandible osteoblasts cells (mOB cells) and periodontal ligament cells (PDLCs). It has a relatively low but still noticeable amount of expression in prostate cancer cell line (PC3). It is observed to be expressed in the extracellular matrix (ECM) around the mOB cells, and it is suggested that RLIG1 protein is imported and embedded into ECM from mOB cells. RLIG1 are also discovered in the area around mineralization zone of the growth plate and calcified cartilage of trabecular bone in rats. RLIG1 is a potential structural protein in skeletal tissue with a role in the extracellular matrix of articular and growth cartilage. It might be decorated with glycosaminoglycans, thus a potential proteoglycan.

Cancer RLIG1 is expressed in the most common subtypes (osteoblastic type, mixed osteoblastic/chondroblastic type, and chondroblastic type) of osteosarcoma (OS) patients and humanized OS model. It has a role in promoting the development of the musculoskeletal system. RLIG1 has a significantly high expression in the tumor cells, but its expression is not associated with the proliferation of the tumors. OS located at the jaw or temporal regions has a statistically significant expression of RLIG1 than OS in the extremity or trunk region. C12orf29 expression has a strong positive correlation with the expression of Ki67 gene (a biomarker for tumor proliferation).

KLF9 The mRNA expression of RLIG1 protein is increased with Krüppel-like factor 9 (KLF9) suppression.KLF9 is a transcriptional regulator of uterine endometrial cell proliferation, adhesion, and differentiation, which are essential processes for pregnancy success. KLF9 expression is suppressed during tumorigenesis.

References