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Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs.

ABSTRACT: Deep sequencing studies frequently identify small RNA fragments of abundant RNAs. These fragments are thought to represent degradation products of their precursors. Using sequencing, computational analysis, and sensitive northern blot assays, we show that constitutively expressed non-coding RNAs such as tRNAs, snoRNAs, rRNAs and snRNAs preferentially produce small 5' and 3' end fragments. Similar to that of microRNA processing, these terminal fragments are generated in an asymmetric manner that predominantly favors either the 5' or 3' end. Terminal-specific and asymmetric processing of these small RNAs occurs in both mouse and human cells. In addition to the known processing of some 3' terminal tRNA-derived fragments (tRFs) by the RNase III endonuclease Dicer, we show that several RNase family members can produce tRFs, including Angiogenin that cleaves the T?C loop to generate 3' tRFs. The 3' terminal tRFs but not the 5' tRFs are highly complementary to human endogenous retroviral sequences in the genome. Despite their independence from Dicer processing, these tRFs associate with Ago2 and are capable of down regulating target genes by transcript cleavage in vitro. We suggest that endogenous 3' tRFs have a role in regulating the unwarranted expression of endogenous viruses through the RNA interference pathway.

SUBMITTER: Li Z

PROVIDER: S-EPMC3413118 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs.

Li Zhihua Z Ender Christine C Meister Gunter G Moore Patrick S PS Chang Yuan Y John Bino B

Nucleic acids research 20120409 14

Deep sequencing studies frequently identify small RNA fragments of abundant RNAs. These fragments are thought to represent degradation products of their precursors. Using sequencing, computational analysis, and sensitive northern blot assays, we show that constitutively expressed non-coding RNAs such as tRNAs, snoRNAs, rRNAs and snRNAs preferentially produce small 5' and 3' end fragments. Similar to that of microRNA processing, these terminal fragments are generated in an asymmetric manner that ...[more]

PMID: 22492706

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Project description:Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is a non‐Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor‐specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. Materials and Methods Survival‐related snoRNAs were selected to construct a specific snoRNA‐based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein–protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co‐expressed genes. Results Twelve prognosis‐correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three‐snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high‐risk and low‐risk cohorts using the risk model, and the high‐risk group and activated B cell‐like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co‐expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co‐expressed genes in DLBCL. Conclusion Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction. A comprehensive analysis was performed to select significant survival‐related snoRNAs in DLBCL. Collectively, a prognostic signature based on three snoRNAs (SNORD1A, SNORA60, and SNORA66) was established for DLBCL patients. Also, we found snoRNA co‐expressed genes that were mostly involved in ribosome‐correlated pathways and processes, and the interaction of ribosomal proteins (RPL23, RPL10A) and p53.

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Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs.

Publications

Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs.

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