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Review
. 2002;10(1-2):59-78.

The 3' end formation in small RNAs

Karthika Perumal  1 , Ram Reddy
Affiliations
Review

The 3' end formation in small RNAs

Karthika Perumal et al. Gene Expr. 2002.

Abstract

Small RNAs are a major class of RNAs along with transfer RNAs, ribosomal RNAs, and messenger RNAs. They vary in size from less than 100 nucleotides to several thousand nucleotides and have been identified and characterized both in prokaryotes and eukaryotes. Small RNAs participate in a variety of cellular functions including regulating RNA synthesis, RNA processing, guiding modifications in RNA, and in transport of proteins. Small RNAs are generated by a series of posttranscriptional processing steps following transcription. While RNA 5' end structure, 5' cap formation, and RNA processing mechanisms have been fairly well characterized, the 3' end processing is poorly understood. Recent data point to an emerging theme in small RNAs metabolism in which the 3' end processing is mediated by the exosome, a large multienzyme complex. In addition to removal of nucleotides by the exosome, there is simultaneous rebuilding of the 3' end of some small RNA by adenylation and/or uridylation. This review presents a picture of both degradative and rebuilding reactions operative on the 3' end of some small RNA molecules in prokaryotes and eukaryotes.

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Figures

Figure 1
Figure 1
The 3′ end formation in human U1 snRNA. The sequence corresponding to the mature human U1 RNA (nucleotides 1–164) is shown in pink. The 3′ box (shown in brown) is 14 nucleotides long and is 11 nucleotides downstream of the mature 3′ end. The pacman represents the exosome complex.
Figure 2
Figure 2
The 3′ end formation of intronic snoRNAs in eukaryotes. Intron-encoded snoRNAs (pink box) are transcribed as a part of a pre-mRNA. Green boxes indicate exons. The snoRNA is released from the rest of the intron by two possible ways. In the first pathway, the intron lariat, formed by splicing, is linearized by a debranching activity. 5′ end processing is carried out by 5′→3′ exonucleases (green pacman), while the 3′→5′ exonucleases organized in the exosome complex (orange pacman) trim the 3′ end trailer sequence to form the mature 3′ end. In the alternate pathway, endonucleolytic cleavages (blue arrows) upstream and downstream of the snoRNA release the snoRNA. The mature 5′ and 3′ ends are generated by exonucleases, similar to the first processing pathway.
Figure 3
Figure 3
The 3′ end formation of polycistronic snoRNAs in eukaryotes. Polycistronic snoRNAs are transcribed by a common upstream promoter. Individual snoRNAs (pink box) are released by the action of endonucleases upstream and downstream of the snoRNA sequence. 5′→3′ exonucleases and 3′→5′ exonucleases trim the 5′ leader and 3′ trailer sequences to generate the mature 5′ and 3′ ends of the snoRNA.
Figure 4
Figure 4
A model for the trimming, 2′,3′-cyclic phosphate (>p) formation, and addition of nucleotides to the 3′ end of U6 snRNA. The removal of nucleoside involves cleavage of ester bond between 3′-phosphate and 5′-hydroxyl group. The asterisks indicate 32P-labeled phosphate residues derived from [α-32P]UTP.
Figure 5
Figure 5
A model for the adenylation and turnover of posttranscriptionally added adenylic acid in SRP RNA. The secondary structure of SRP and Alu RNAs has been studied by several investigators (141). SRP 9/14 protein heterodimer was shown to bind in this region of SRP RNA (127,144). The relative size and sites of binding of SRP 9/14 protein heterodimer are shown only for the purpose of illustration. Broken arrow represents a possible alternate pathway for the transport of SRP RNA without the 3′ end adenylation.
Figure 6
Figure 6
A model depicting the 3′ end deletions/additions occurring on the 3′ end of human small RNAs. All available evidence is in support of this model. The RNAs bind with appropriate proteins to form the ribonucleoprotein particles. The 3′ ends of RNAs are trimmed where one or more nucleotides are removed. These RNAs can be rebuilt by uridylation; thus, this reaction is reversible. The RNAs are also adenylated and deadenylated; this reaction also is reversible. The RNAs containing adenylic acid residues cannot be uridylated. This reaction is not reversible. RNAs containing adenylic acid on the 3′ end have to be first deadenylated before further uridylation can take place.
Figure 7
Figure 7
The 3′ end formation in yeast U1 snRNA. U1 snRNA in S. cerevisiae is made as a precursor with ∼120 extra nucleotides on the 3′ end. There are two alternate pathways for generating the mature 3′ end (114). One of the pathways is dependent on Rnt1p, an endonuclease with homology to RNase III, while the second pathway is independent of Rnt1p. Both of these maturation pathways are dependent on the 3′-terminal Sm site and associated proteins. In the Rnt1p-dependent pathway, there are two prominent intermediates: a nonpolyadenylated RNA, extending 64–78 nucleotides beyond the mature 3′ end, and the related polyadenylated RNA.
Figure 8
Figure 8
The 3′ end formation in two bacterial RNAs: ribosomal 5S RNA and tmRNA. (A) 5S rRNA (purple box) is synthesized as part of a polycistronic primary transcript that contains the other two ribosomal RNAs, 16S and the 18S rRNAs (green boxes). The endonuclease RNase III cleaves the primary transcript to separate the individual rRNAs. Another endonuclease RNase E cleaves the 5S RNA precursor at about three nucleotides away from the mature 3′ end (128). The exoribonuclease RNase T trims the final three nucleotides to generate the mature 3′ end (77). (B) Pre-tmRNA is folded into a pre-tRNA-like structure in vivo such that it can be cleaved by RNase P to generate the 5′ end of the mature tmRNA. The 3′ trailer sequence is acted upon by endoribonuclease RNase III. The final exonucleolytic trimming by RNase T yields the mature 3′ end –CCA. It has also been shown that the final 3′ end could be obtained by endonucleolytic cleavage by RNase E. (C) Sequence and structure near the 3′ end of 5S RNA and tmRNA (77). Nucleotides present in the mature RNA are shown in black letters while the nucleotides that are removed by the final exonucleolytic trimming are shown in orange letters. Arrows indicate the direction of trimming by RNase T.
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