Crystal structures of a group II intron maturase reveal a missing link in spliceosome evolution

Abstract

Group II introns are self-splicing ribozymes that are essential in many organisms, and they are hypothesized to share a common evolutionary ancestor with the spliceosome. While structural similarity of RNA components supports this connection, it is of interest to determine whether associated protein factors also share an evolutionary heritage. Here we present the crystal structures of reverse transcriptase (RT) domains from two group II intron encoded proteins (maturases) from Roseburia intestinalis and Eubacterium rectale, obtained at 1.2 Å and 2.1 Å respectively. Their architecture is more similar to the spliceosomal Prp8 RT-like domain than to any other RTs, and they share substantial similarity with flaviviral RNA polymerases. The RT domain itself is sufficient for binding intron RNA with high affinity and specificity, and it is contained within an active RT enzyme. These studies provide a foundation for understanding structure-function relationships within group II intron–maturase complexes.

Forks in the tracks: Group II introns, spliceosomes, telomeres and beyond

“…A similarity of RIM to TERT also became apparent when the RT0 motif was removed from the analysis. 5 Furthermore, whereas the fingers-palm RT1-RT7 of LtrA is related to TERT, the RIM structure of this domain shares substantial resemblance to the flaviviral hepatitis C virus RNA polymerase.…”

“…From purely sequence-based comparisons, distinctive classes of group II introns, retroviruses, viral polymerases, TERT and other retroelements emerge, 11-13 but the structure-based alignments give few clues as to ancestral origins, given the paucity of solved structures. Nevertheless, an unbiased comparison of the overall RMSD values for the structure of the RT domains (RT0-RT7) in RIM 5 and LtrA 4 with the structure of the RT domain in various related proteins finds HCV (PDB ID: 1C2P) with an RMSD of 2.2 A and TERT (PDB ID: 3KYL) with an RMSD of 2.0 A , respectively, as their closest matches.…”

“…Simultaneously, 2 structures of the fingers-palm domain alone of the RT from Roseburia intestinalis (Ri) and Eubacterium rectale (Er) bacteria were solved at 1.2 and 2.2 A resolution, respectively. 5 These two structures, referred to as maturases, encompass the RT0-RT7 motifs and include the NTE and fingers-palm domain, but not the thumb domain. The 2 structures are almost identical and the focus is therefore on Ri maturase (RIM), which is of exceptional resolution.…”

“…Now studies of group II intron-encoded proteins (IEPs) add an additional layer of similarity, not only very strikingly to the spliceosome, but also to other extant ribonucleoprotein (RNP) machines like viruses and telomerases. 4,5 RNP and protein structures illuminate RNA-protein interactions While previous efforts have revealed the structure of a group IIA intron at low resolution, 6-8 the recent breakthrough to solve the group IIA intron RNA from Lactococcus lactis in complex with the intron encoded protein (IEP) provides a first nearatomic model of the overall architecture of a group II intron RNP (Fig. 1A).…”

“…Now studies of group II intron-encoded proteins (IEPs) add an additional layer of similarity, not only very strikingly to the spliceosome, but also to other extant ribonucleoprotein (RNP) machines like viruses and telomerases. 4,5 …”