DNA-methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used clinically to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERVs), which can induce immune response by acting as cellular double-stranded RNAs (dsRNAs). Yet, the posttranscriptional regulation of ERV dsRNAs remains uninvestigated. Here, we find that the viral mimicry and subsequent cell death in response to decitabine require the dsRNA-binding protein Staufen1 (Stau1). We show that Stau1 directly binds to ERV RNAs and stabilizes them in a genome-wide manner. Furthermore, Stau1-mediated stabilization requires a long noncoding RNA TINCR, which enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that MDS and AML patients with lower Stau1 and TINCR expressions exhibit inferior treatment outcomes to DNMTi therapy. Overall, our study reveals the posttranscriptional regulatory mechanism of ERVs and identifies the Stau1-TINCR complex as a potential target for predicting the efficacy of DNMTis and other drugs that rely on dsRNAs.

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키워드 : 파이프라이닝, 임베디드 데이터베이스, 질의 처리기 Block-wise Skipping for Embedded Database SystemToday, most of all the query processors in the world generally use the 'Pipelining' method to acquire fast response time (first record latency) and less memory usage. Each of the operator nodes in the Query Execution Plan (QEP) provides Open(), Next(), and Close() functions for their interface to facilitate the iterator mechanism. However, the embedded database systems for the mobile devices, based on the FLASH memory, usually require a function like Previous(), which returns the previous records from current position. It is because that, in the embedded environment, the mobile devices cannot fully provide it main memory to store all the query results. So, whenever needed the previously read records the user (program) should re-fetch the previous records using the Previous() function: the BACKWARD data fetch. In this paper, I introduce the 'Direction Switching Problem' caused by the Previous() function and suggest 'Block-wise Skipping' method to fully utilize the benefits of the block-based data transfer mechanism, which is widely accepted by most of the today's relational database management systems.