Ribonucleoprotein multimers and their functions

Abstract

Ribonucleoproteins (RNPs) play key roles in many cellular processes and often function as RNP enzymes. Similar to proteins, some of these RNPs exist and function as multimers, either homomeric or heteromeric. While in some cases the mechanistic function of multimerization is well understood, the functional consequences of multimerization of other RNPs remain enigmatic. In this review we will discuss the function and organization of small RNPs that exist as stable multimers, including RNPs catalyzing RNA chemical modifications, telomerase RNP, and RNPs involved in pre-mRNA splicing.

Figure 1

Architecture of box C/D s(no)RNPs. A) Box C/D s(no)RNAs contain conserved sequences, named boxes C, D, C′, and D′. The spacer sequences between boxes C and D′ as well as between boxes C′ and D contain guide sequences that are complementary to the substrate RNAs targeted for methylation. The 5′ and 3′ sequences usually form a terminal stem. B) Conventional mono-sRNP model for archaeal box C/D sRNPs. According to this model, archaeal box C/D sRNPs are composed of one sRNA molecule and two copies of each of the three archaeal box C/D core proteins, assembled symmetrically on the sRNA. C) Di-sRNP model of archaeal box C/D sRNP architecture. According to this structure-based model, archaeal box C/D sRNPs contain two RNA molecules and four sets of each core protein. Colors are: grey - RNA, yellow - L7Ae, blue - Nop5, orange - fibrillarin. D) EM structure of a M. jannaschii box C/D sRNP (EMD-1636, Bleichert et al., 2009) with fitted crystal structures of core proteins (PDB 2nnw, Oruganti et al., 2007; PDB 1xbi, Suryadi et al., 2005). Figures 1A–D are reprinted from (Bleichert et al., 2009). E) and F) Asymmetric assembly models of eukaryotic box C/D mono and di-snoRNP architecture, respectively. Colors are: grey -RNA, yellow - 15.5K/Snu13, light blue - Nop56, dark blue - Nop58, orange - fibrillarin. A color version of this figure is available online.

Figure 2

Telomerase RNP function. A) Domain organization of telomerase reverse transcriptase (TERT). B) Repeat addition cycle for telomerase. Telomerase RNA base pairs to 3′ single stranded overhangs of chromosome ends and TERT reverse transcribes the template sequence into the telomeric DNA. Once the template boundary is reached, telomerase can translocate and catalyze the addition of another telomere repeat, which involves realignment of the 3′ template sequence of telomerase RNA with the newly synthesized repeat sequence. A color version of this figure is available online.

Figure 3

Assembly and recycling of U4/U6.U5 tri-snRNP during pre-mRNA splicing. The U4/U6 di-snRNP is formed by association of the U4 and U6 snRNPs through base pairing of their snRNA components. Subsequently, the U5 snRNP joins to form the U4/U6.U5 tri-snRNP. Recruitment of the U4/U6.U5 tri-snRNPs into the spliceosome results in formation of the B complex. Activation of the spliceosome requires structural rearrangements that result in release of the U4 snRNP and the U6 snRNA associated Lsm2-8 proteins. After splicing is completed, U5 and U6 snRNPs are recycled, joining the U4 snRNP to form U4/U6 di-snRNPs and U4/U6.U5 tri-snRNPs, respectively. A color version of this figure is available online.

Figure 4

Composition of the human U4/U6.U5 tri-sRNP. U4/U6 di-snRNP (orange) and U5 snRNP (blue) associate to form the U4/U6.U5 tri-snRNP. Proteins specific to the tri-snRNP that are not found in the U4/U6 di-snRNP or U5 snRNP are shown in yellow. Protein-protein interactions within and between RNPs are indicated by solid lines. Known snRNA-protein interactions are indicated by arrows. The U4 and U6 snRNAs are base paired in both the U4/U6 di-snRNP and the U4/U6.U5 tri-sRNP. Proteins are conserved in yeast except for 27K, 40K, and hCypH. A color version of this figure is available online.