SECIS element

In bacteria the SECIS element appears soon after the UGA codon it affects. In archaea and eukaryotes, it occurs in the 3' UTR of an mRNA, and can cause multiple UGA codons within the mRNA to code for selenocysteine. One archaeal SECIS element, in Methanococcus, is located in the 5' UTR. In any case, it serves to recruit EEFSEC or SelB, the specialized homolog of EF-Tu/eEF1&alpha, with the ability to read tRNA^Sec.{{cite journal | vauthors = Wilting R, Schorling S, Persson BC, Böck A | title = Selenoprotein synthesis in archaea: identification of an mRNA element of Methanococcus jannaschii probably directing selenocysteine insertion | journal = Journal of Molecular Biology | volume = 266 | issue = 4 | pages = 637–641 | date = March 1997 | pmid = 9102456 | doi = 10.1006/jmbi.1996.0812 }}{{cite journal | vauthors = Rother M, Resch A, Wilting R, Böck A | title = Selenoprotein synthesis in archaea | journal = BioFactors | volume = 14 | issue = 1–4 | pages = 75–83 | date = 2001 | pmid = 11568443 | doi = 10.1002/biof.5520140111 }}

The SECIS elements appear defined by sequence characteristics (particular nucleotides tend to be at particular positions in it), and a characteristic bent-hairpin secondary structure due to base-pairing of complementary RNA nucleotides. Although the eukaryotic, archaeal and bacterial SECIS elements each share a general hairpin structure, they are not alignable, e.g. an alignment-based scheme to recognize eukaryotic SECIS elements will not be able to recognize archaeal SECIS elements.

Bacterial SECIS is recognized by SelB. Each element targets one UGA codon. Rfam provides three separate groups of bacterial SECIS.

Eukaryotic SECIS elements are recognized by SBP2, which in turn binds EEFSEC to provide for elongation. In most cases the "kink-turn" part bound to SBP2 has a very conserved sequence "AUGA", but "GGGA" has also been found. 60S ribosomal protein L30 also recognizes SECIS, though its role is less well-understood.{{cite journal |last1=Allmang |first1=C. |last2=Krol |first2=A. |title=Selenoprotein synthesis: UGA does not end the story |journal=Biochimie |date=November 2006 |volume=88 |issue=11 |pages=1561–1571 |doi=10.1016/j.biochi.2006.04.015|pmid=16737768 }}

The eukaryotic SECIS element consists of a small stem, a "kink-turn" core with AUGA/GGGA, another stem, and a terminal loop of 5-30 nt. In "Group II" SECIS elements the terminal loop is interrupted by a stem. The eukaryotic SECIS element includes wobble A-G base pairs, which are uncommon in nature, but are critically important for correct SECIS element function.

Rfam provides two groups of eukaryotic SECIS. SECIS_1 is built from animal sequences. SECIS_5 is built from Plasmodium sequences.

It is unclear which piece of the archaeal translation machinery is responsible for recognizing SECIS. They have a version of SelB/EEFSEC, but it has neither the bacterial SECIS-recognizing expansion nor the eukaryotic RBP2-recognizing expansion.

Archaeal SECIS consists of a "base" stem ending in GC-rich pairs, a conserved bulge region, a small (3bp) GC-rich stem, and a terminal AT-rich loop of 3-8 nt.

Lokiarcheota, a group of archaea believed to be related to the archaeal ancestor of eukaryotes, use eukaryotic-like kink-turn "AUGA" SECIS elements with no conserved bulge on a few families of selenoproteins. This type is believed to have evolved from the SECIS element from archaeal VhuD proteins, which also has a "AUGA" part but is not predicted to form a kink-turn. Lokiarcheota have no identified version of SBP2, but they do have L30.{{cite journal|last1=Mariotti|first1=Marco|last2=Lobanov|first2=Alexei V.|last3=Manta|first3=Bruno|last4=Santesmasses|first4=Didac|last5=Bofill|first5=Andreu|last6=Guigó|first6=Roderic|last7=Gabaldón|first7=Toni|last8=Gladyshev|first8=Vadim N.|title=Lokiarchaeota Marks the Transition between the Archaeal and Eukaryotic Selenocysteine Encoding Systems|journal=Molecular Biology and Evolution|volume=33|issue=9|year=2016|pages=2441–2453|issn=0737-4038|doi=10.1093/molbev/msw122|pmid=27413050|pmc=4989117|doi-access=free}}

SECIS elements can be found using the sequence and secondary structure characteristics of groups of known SECIS elements. Methods are open-source unless specifically noted.

• The ERPIN program for RNA motif search was used to find new SECIS elements in animals, resulting in the identification of novel families of selenoproteins.{{cite journal | vauthors = Lambert A, Lescure A, Gautheret D | title = A survey of metazoan selenocysteine insertion sequences | journal = Biochimie | volume = 84 | issue = 9 | pages = 953–959 | date = September 2002 | pmid = 12458087 | doi = 10.1016/S0300-9084(02)01441-4 }}
• Rfam provides five pre-built profiles for the Infernal RNA covariance search program as well as matches in GenBank sequences.
• SECISearch3 is broadly applicable to eukaryotes. It starts by finding candidates using three existing methods, Infernal, Covels, and SECISearch. It then merges the candidates, refines their structures, and filters the structures for hard-coded constraints. Both SECISearch3 and SECISearch are closed source and accessible through web services only.{{cite journal |last1=Mariotti |first1=M |last2=Lobanov |first2=AV |last3=Guigo |first3=R |last4=Gladyshev |first4=VN |title=SECISearch3 and Seblastian: new tools for prediction of SECIS elements and selenoproteins. |journal=Nucleic acids research |date=August 2013 |volume=41 |issue=15 |pages=e149 |doi=10.1093/nar/gkt550 |pmid=23783574}} SECISearch3 is the best method for eukaryotes as of 2020.{{cite journal |last1=Santesmasses |first1=D |last2=Mariotti |first2=M |last3=Gladyshev |first3=VN |title=Bioinformatics of Selenoproteins. |journal=Antioxidants & redox signaling |date=1 September 2020 |volume=33 |issue=7 |pages=525-536 |doi=10.1089/ars.2020.8044 |pmid=32031018}} The identification of SECIS elements remains difficult in eukaryotes, especially non-animal ones.
• bSECISearch uses a RNAfold-based method similar to the original SECISearch to find bacterial SECIS. It is closed source and accessible through web services only.
• A version of SECISearch was adapted for the archaeal SCEIS consensus. This version is neither available as a download nor as an online service.{{cite journal |last1=Kryukov |first1=GV |last2=Gladyshev |first2=VN |title=The prokaryotic selenoproteome. |journal=EMBO reports |date=May 2004 |volume=5 |issue=5 |pages=538-43 |doi=10.1038/sj.embor.7400126 |pmid=15105824}}

New families of selenoproteins have been found by searching for SECIS elements and checking the associated protein-coding region for UGA.

New types of SECIS elements have been found by searching for protein-coding regions homologous to known selenoproteins, then checking the 3' UTR for secondary structure.

• An unusual "GGGA" type of SECIS element was found in Toxoplasma and Neospora for their version of selenoprotein T.{{cite journal |last1=Novoselov |first1=SV |last2=Lobanov |first2=AV |last3=Hua |first3=D |last4=Kasaikina |first4=MV |last5=Hatfield |first5=DL |last6=Gladyshev |first6=VN |title=A highly efficient form of the selenocysteine insertion sequence element in protozoan parasites and its use in mammalian cells. |journal=Proceedings of the National Academy of Sciences of the United States of America |date=8 May 2007 |volume=104 |issue=19 |pages=7857-62 |doi=10.1073/pnas.0610683104 |pmid=17470795}}

The SECIS element is found in a wide variety of organisms from all three domains of life (including their viruses).{{cite journal | vauthors = Mix H, Lobanov AV, Gladyshev VN | title = SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes | journal = Nucleic Acids Research | volume = 35 | issue = 2 | pages = 414–423 | year = 2007 | pmid = 17169995 | pmc = 1802603 | doi = 10.1093/nar/gkl1060 }}{{cite journal | vauthors = Cassago A, Rodrigues EM, Prieto EL, Gaston KW, Alfonzo JD, Iribar MP, Berry MJ, Cruz AK, Thiemann OH | title = Identification of Leishmania selenoproteins and SECIS element | journal = Molecular and Biochemical Parasitology | volume = 149 | issue = 2 | pages = 128–134 | date = October 2006 | pmid = 16766053 | doi = 10.1016/j.molbiopara.2006.05.002 }}{{cite journal | vauthors = Mourier T, Pain A, Barrell B, Griffiths-Jones S | title = A selenocysteine tRNA and SECIS element in Plasmodium falciparum | journal = RNA | volume = 11 | issue = 2 | pages = 119–122 | date = February 2005 | pmid = 15659354 | pmc = 1370700 | doi = 10.1261/rna.7185605 }}{{cite journal | vauthors = Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigó R, Gladyshev VN | title = Characterization of mammalian selenoproteomes | journal = Science | volume = 300 | issue = 5624 | pages = 1439–1443 | date = May 2003 | pmid = 12775843 | doi = 10.1126/science.1083516 | bibcode = 2003Sci...300.1439K | s2cid = 10363908 | name-list-style = amp | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1072&context=biochemgladyshev | url-access = subscription }}{{cite journal | vauthors = Kryukov GV, Gladyshev VN | title = The prokaryotic selenoproteome | journal = EMBO Reports | volume = 5 | issue = 5 | pages = 538–543 | date = May 2004 | pmid = 15105824 | pmc = 1299047 | doi = 10.1038/sj.embor.7400126 | name-list-style = amp }}{{cite journal | vauthors = Krol A | title = Evolutionarily different RNA motifs and RNA-protein complexes to achieve selenoprotein synthesis | journal = Biochimie | volume = 84 | issue = 8 | pages = 765–774 | date = August 2002 | pmid = 12457564 | doi = 10.1016/S0300-9084(02)01405-0 }}

{{reflist}}

• {{Rfam|id=RF00031|name=SECIS element 1}}
• {{Rfam|id=RF01988|name=SECIS element 2}}
• {{Rfam|id=RF01989|name=SECIS element 3}}
• {{Rfam|id=RF01990|name=SECIS element 4}}
• {{Rfam|id=RF01991|name=SECIS element 5}}

Category:Gene expression

Category:Cis-regulatory RNA elements