Small nucleolar RNAs controlling rRNA processing in Trypanosoma brucei

Abstract

In trypanosomes, in contrast to most eukaryotes, the large subunit (LSU) ribosomal RNA is fragmented into two large and four small ribosomal RNAs (srRNAs) pieces, and this additional processing likely requires trypanosome-specific factors. Here, we examined the role of 10 abundant small nucleolar RNAs (snoRNAs) involved in rRNA processing. We show that each snoRNA involved in LSU processing associates with factors engaged in either early or late biogenesis steps. Five of these snoRNAs interact with the intervening sequences of rRNA precursor, whereas the others only guide rRNA modifications. The function of the snoRNAs was explored by silencing snoRNAs. The data suggest that the LSU rRNA processing events do not correspond to the order of rRNA transcription, and that srRNAs 2, 4 and 6 which are part of LSU are processed before srRNA1. Interestingly, the 6 snoRNAs that affect srRNA1 processing guide modifications on rRNA positions that span locations from the protein exit tunnel to the srRNA1, suggesting that these modifications may serve as check-points preceding the liberation of srRNA1. This study identifies the highest number of snoRNAs so far described that are involved in rRNA processing and/or rRNA folding and highlights their function in the unique trypanosome rRNA maturation events.

Nucleolar Structure and Function in Trypanosomatid Protozoa

“…In most organisms, a small subset of around six snoRNAs participates in rRNA processing, including the box C/D snoRNAs U3, U8, U14 and U22, and the box H/ACA snoRNAs U17 (snR30) and snR10 [92]. Remarkably, at least 18 snoRNAs (16 box C/D and 2 box H/ACA) are involved in rRNA processing in trypanosomatids, which is the highest number ever reported [117]. This is in accordance with the extensive processing required to produce the six independent rRNA species from the LSU precursor in trypanosomatids (Figure 3).…”

“…This is in accordance with the extensive processing required to produce the six independent rRNA species from the LSU precursor in trypanosomatids (Figure 3). As anticipated, several of these snoRNAs are exclusive to trypanosomatids [117]. In yeast, U3 snoRNA is required for early processing events conducting to 18S rRNA maturation, as it participates in cleavage at A0, A1 and A2 sites [106].…”

“…Similarly to other organisms, box H/ACA snR30 (U17) and MRP snoRNA participate in early processing of the rRNA precursor in T. brucei [109,110]. Other snoRNAs involved in rRNA processing in T. brucei are: TB11Cs2C1 (U31), TB11Cs2C2, TB10Cs4C4, TB6Cs1C3, TB9Cs2C1, TB9Cs2C5 (snR60), TB9Cs3C3, TB10Cs4C3, TB11Cs3C2, TB10Cs1C4 (snR75), TB10Cs1C1 (snR64), TB8Cs1C1, TB8Cs1C3, TB9Cs2C3 (snR39b) and TB9Cs3H2 (Atsnor77, a box H/ACA snoRNA) [117,120,121]. Some of these snoRNAs are not directly involved in cleavage, but guide modifications required for rRNA processing.…”

“…Next, a cleavage within ITS5 separates the two large rRNAs (24Sα and 24Sβ) and sr1 from the three distal small rRNAs (sr2, sr4, and sr6) (Figure 3) [119,125,126]. Though the remaining steps to produce the mature rRNA molecules have yet to be established, recent data indicate that sr1 is the last LSU rRNA to be processed [117,127].…”

Identification of a novel small nucleolar RNAs prognostic signature for patients with acute myelocytic leukemia

“…Small nucleolar RNA (snoRNA) is also a class of non-coding RNA, with a length of 60-30nt. As early studies found that snoRNA was mainly located in the nucleoli and was related to the processing and modi cation of rRNA, its function was relatively simple [9][10][11]. However, in recent years, more and more RNA sequencing (RNA-seq) dataset show that snoRNA shows a general trend of high expression in tumors, and some studies show that snoRNA is involved in the occurrence, progression and prognosis of tumors, and may be a kinds of new clinical biomarkers [12][13][14].…”