m6A: Signaling for mRNA splicing

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Among myriads of distinct chemical modifications in RNAs, dynamic N6-methyladenosine (m(6)A) is one of the most prevalent modifications in eukaryotic mRNAs and non-coding RNAs. Similar to the critical role of chemical modifications in regulation of DNA and protein activities, RNA m(6)A modification is also observed to be involved in the regulation of diverse functions of RNAs including meiosis, fertility, development, cell reprogramming and circadian period. The RNA m(6)A modification is recognized by YTH domain containing family proteins comprising of YTHDC1-2 and YTHDF1-3. Here we focus on the nuclear m(6)A reader YTHDC1 and its regulatory role in alternative splicing and other RNA metabolic processes.

Related collections

Most cited references 4

Record: found
Abstract: found
Article: not found

An amazing sequence arrangement at the 5' ends of adenovirus 2 messenger RNA.

Louise Chow, Richard E. Gelinas, Thomas R. Broker … (1977)

The 5' terminal sequences of several adenovirus 2 (Ad2) mRNAs, isolated late in infection, are complementary to sequences within the Ad2 genome which are remote from the DNA from which the main coding sequence of each mRNA is transcribed. This has been observed by forming RNA displacement loops (R loops) between Ad2 DNA and unfractionated polysomal RNA from infected cells. The 5' terminal sequences of mRNAs in R loops, variously located between positions 36 and 92, form complex secondary hybrids with single-stranded DNA from restriction endonuclease fragments containing sequences to the left of position 36 on the Ad2 genome. The structures visualized in the electron microscope show that short sequences coded at map positions 16.6, 19.6 and 26.6 on the R strand are joined to form a leader sequence of 150-200 nucleotides at the 5' end of many late mRNAs. A late mRNA which maps to the left of position 16.6 shows a different pattern of second site hybridization. It contains sequences from 4.9-6.0 linked directly to those from 9.6-10.9. These findings imply a new mechanism for the biosynthesis of Ad2 mRNA in mammalian cells.

0 comments Cited 207 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The YTH domain is a novel RNA binding domain.

Stefan Stamm, Janusz Bujnicki, Dominik Theler … (2010)

The YTH (YT521-B homology) domain was identified by sequence comparison and is found in 174 different proteins expressed in eukaryotes. It is characterized by 14 invariant residues within an alpha-helix/beta-sheet structure. Here we show that the YTH domain is a novel RNA binding domain that binds to a short, degenerated, single-stranded RNA sequence motif. The presence of the binding motif in alternative exons is necessary for YT521-B to directly influence splice site selection in vivo. Array analyses demonstrate that YT521-B predominantly regulates vertebrate-specific exons. An NMR titration experiment identified the binding surface for single-stranded RNA on the YTH domain. Structural analyses indicate that the YTH domain is related to the pseudouridine synthase and archaeosine transglycosylase (PUA) domain. Our data show that the YTH domain conveys RNA binding ability to a new class of proteins that are found in all eukaryotic organisms.

0 comments Cited 123 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn).

S. Stamm, Hans Schwaiger, A Obermeier … (1999)

Alternative pre-mRNA splicing patterns can change an extracellular stimulus, but the signaling pathways leading to these changes are still poorly characterized. Here, we describe a tyrosine-phosphorylated nuclear protein, YT521-B, and show that it interacts with the nuclear transcriptosomal component scaffold attachment factor B, and the 68-kDa Src substrate associated during mitosis, Sam68. Northern blot analysis demonstrated ubiquitous expression, but detailed RNA in situ analysis revealed cell type specificity in the brain. YT521-B protein is localized in the nucleoplasm and concentrated in 5-20 large nuclear dots. Deletion analysis demonstrated that the formation of these dots depends on the presence of the amino-terminal glutamic acid-rich domain and the carboxyl-terminal glutamic acid/arginine-rich region. We show that the latter comprises an important protein-protein interaction domain. The Src family kinase p59(fyn)-mediated tyrosine phosphorylation of Sam68 negatively regulates its association with YT521-B, and overexpression of p59(fyn) dissolves nuclear dots containing YT521-B. In vivo splicing assays demonstrated that YT521-B modulates alternative splice site selection in a concentration-dependent manner. Together, our data indicate that YT521-B and Sam68 may be part of a signal transduction pathway that influences splice site selection.