lncRNAs transactivate Staufen1-mediated mRNA decay by duplexing with 3'UTRs via Alu elements

By Chenguang Gong, L. Maquat. Nature, 2011

1,189 citations recorded by the source corpus.

Staufen 1 (STAU1)-mediated messenger RNA decay (SMD) involves the degradation of translationally active mRNAs whose 3′-untranslated regions (3′ UTRs) bind to STAU1, a protein that binds to double-stranded RNA. Earlier studies defined the STAU1-binding site within ADP-ribosylation factor 1 (ARF1) mRNA as a 19-base-pair stem with a 100-nucleotide apex. However, we were unable to identify comparable structures in the 3′ UTRs of other targets of SMD. Here we show that STAU1-binding sites can be formed by imperfect base-pairing between an Alu element in the 3′ UTR of an SMD target and another Alu element in a cytoplasmic, polyadenylated long non-coding RNA (lncRNA). An individual lncRNA can downregulate a subset of SMD targets, and distinct lncRNAs can downregulate the same SMD target. These are previously unappreciated functions of non-coding RNAs and Alu elements. Not all mRNAs that contain an Alu element in the 3′ UTR are targeted for SMD even in the presence of a complementary lncRNA that targets other mRNAs for SMD. Most known trans-acting RNA effectors consist of fewer than 200 nucleotides, and these include small nucleolar RNAs and microRNAs. Our finding that the binding of STAU1 to mRNAs can be transactivated by lncRNAs uncovers an unexpected strategy that cells use to recruit proteins to mRNAs and mediate the decay of these mRNAs. We name these lncRNAs half-STAU1-binding site RNAs (1/2-sbsRNAs).

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e3bbdeeddb988860e5bbf2766424c859ee26a467

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Citations in the corpus

LncRNA: a link between RNA and cancer. (2014, neutral): “inducing target mRNA decay (Fig 1j) [39].”
A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA (2011, neutral): “In the cytoplasm, lncRNAs were described to transactivate STAU1-mediated mRNA decay by duplexing with 30 UTRs via Alu elements (Gong and Maquat, 2011) or, in the case of pseudogenes, to compete for miRNA binding, thereby modulating the derepression of miRNA targets (Poliseno et al., 2010; Salmena…”
Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs (2013, background): “For example, Alu elements embedded within several human lncRNAs form a group called 1/2sbs-RNAs that base-pair with complementary Alu elements located in the 39-UTR of several proteincoding transcripts to form duplexes creating a binding site for the Staufen1-mediated RNA decay machinery, which in t”
Molecular mechanisms of long noncoding RNAs (2011, methodology): “Repeat Detector: RNA Decay and Staufen Yet another unforeseen function for lncRNAs was uncovered when a group identified several lncRNAs that are important in downregulating subsets of Staufen 1 (STAU1)-mediated messenger RNA decay (SMD) (Gong and Maquat, 2011).”
Long Noncoding RNAs: Past, Present, and Future (2013, background): “…a subset of these mRNA targets contains an Alu element in its 39-UTRs that can base pair with a group of cytoplasmic and polyadenylated lncRNAs, named half-STAU1-binding site RNAs (1/2-sbsRNAs), that contain complementary Alu elements necessary to form the dsRNA structure (Gong and Maquat 2011).”
Linking Long Noncoding RNA Localization and Function. (2016, background): “Moreover, other lncRNAs can also affect mRNA translation in the cytoplasm [42,43].”