6lbk

From Proteopedia

Structure of rat GLD-2 (Terminal nucleotidyltransferase 2, TENT2)

Structural highlights

6lbk is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4956882Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GLD2_RAT Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail. In contrast to the canonical nuclear poly(A) RNA polymerase, it only adds poly(A) to selected cytoplasmic mRNAs. Does not play a role in replication-dependent histone mRNA degradation. Adds a single nucleotide to the 3' end of specific miRNAs, monoadenylation stabilizes and prolongs the activity of some but not all miRNAs.[UniProtKB:Q6PIY7]

Publication Abstract from PubMed

The stability and processing of cellular RNA transcripts are efficiently controlled via non-templated addition of single or multiple nucleotides, which is catalyzed by various nucleotidyltransferases including poly(A) polymerases (PAPs). Germline development defective 2 (GLD-2) is among the first reported cytoplasmic non-canonical PAPs that promotes the translation of germline-specific mRNAs by extending their short poly(A) tails in metazoan, such as Caenorhabditis elegans and Xenopus. On the other hand, the function of mammalian GLD-2 seems more diverse, which includes monoadenylation of certain microRNAs. To understand the structural basis that underlies the difference between mammalian and non-mammalian GLD-2 proteins, we determine crystal structures of two rodent GLD-2s. Different from C. elegans GLD-2, mammalian GLD-2 is an intrinsically robust PAP with an extensively positively charged surface. Rodent and C. elegans GLD-2s have a topological difference in the beta-sheet region of the central domain. Whereas C. elegans GLD-2 prefers adenosine-rich RNA substrates, mammalian GLD-2 can work on RNA oligos with various sequences. Coincident with its activity on microRNAs, mammalian GLD-2 structurally resembles the mRNA and miRNA processor terminal uridylyltransferase 7 (TUT7). Our study reveals how GLD-2 structurally evolves to a more versatile nucleotidyltransferase, and provides important clues in understanding its biological function in mammals.

Structures of mammalian GLD-2 proteins reveal molecular basis of their functional diversity in mRNA and microRNA processing.,Ma XY, Zhang H, Feng JX, Hu JL, Yu B, Luo L, Cao YL, Liao S, Wang J, Gao S Nucleic Acids Res. 2020 Jul 7. pii: 5868340. doi: 10.1093/nar/gkaa578. PMID:32633758^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ma XY, Zhang H, Feng JX, Hu JL, Yu B, Luo L, Cao YL, Liao S, Wang J, Gao S. Structures of mammalian GLD-2 proteins reveal molecular basis of their functional diversity in mRNA and microRNA processing. Nucleic Acids Res. 2020 Jul 7. pii: 5868340. doi: 10.1093/nar/gkaa578. PMID:32633758 doi:http://dx.doi.org/10.1093/nar/gkaa578