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ALYREF links 3'-end processing to nuclear export of nonpolyadenylated mRNAs

ABSTRACT: The RNA-binding protein ALYREF plays key roles in nuclear export and also 3'-end processing of polyadenylated mRNAs, but whether such regulation also extends to non-polyadenylated RNAs is unknown. Replication-dependent (RD)-histone mRNAs are not polyadenylated, but instead end in a stem-loop (SL) structure. Here, we demonstrate that ALYREF prevalently binds a region next to the SL on RD-histone mRNAs. SL-binding protein (SLBP) directly interacts with ALYREF and promotes its recruitment. ALYREF promotes histone pre-mRNA 3'-end processing by facilitating U7-snRNP recruitment through physical interaction with the U7-snRNP-specific component Lsm11. Furthermore, ALYREF, together with other components of the TREX complex, enhances histone mRNA export. Moreover, we show that 3'-end processing promotes ALYREF recruitment and histone mRNA export. Together, our results point to an important role of ALYREF in coordinating 3'-end processing and nuclear export of non-polyadenylated mRNAs.

SUBMITTER: Jing Fan

PROVIDER: S-SCDT-EMBOJ-2018-99910 | biostudies-other |

REPOSITORIES: biostudies-other

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ALYREF links 3'-end processing to nuclear export of non-polyadenylated mRNAs.

Project description:The RNA-binding protein ALYREF plays key roles in nuclear export and also 3'-end processing of polyadenylated mRNAs, but whether such regulation also extends to non-polyadenylated RNAs is unknown. Replication-dependent (RD)-histone mRNAs are not polyadenylated, but instead end in a stem-loop (SL) structure. Here, we demonstrate that ALYREF prevalently binds a region next to the SL on RD-histone mRNAs. SL-binding protein (SLBP) directly interacts with ALYREF and promotes its recruitment. ALYREF promotes histone pre-mRNA 3'-end processing by facilitating U7-snRNP recruitment through physical interaction with the U7-snRNP-specific component Lsm11. Furthermore, ALYREF, together with other components of the TREX complex, enhances histone mRNA export. Moreover, we show that 3'-end processing promotes ALYREF recruitment and histone mRNA export. Together, our results point to an important role of ALYREF in coordinating 3'-end processing and nuclear export of non-polyadenylated mRNAs.

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ALYREF links 3'processing and nuclear export of histone mRNAs

Project description:To examine whether ALYREF can facilitate the 3'processing of RD histone mRNA,we isolated and sequenced the polyadenylated and nonpolyadenylated RNAs from control and ALYREF KD cells

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ALYREF links 3'processing and nuclear export of histone mRNAs

Project description:ALYREF links 3'processing and nuclear export of histone mRNAs

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Polyadenylation and nuclear export of mRNAs.

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IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs.

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YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs.

Project description:N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic messenger RNA (mRNA) and plays critical roles in RNA biology. The function of this modification is mediated by m6A-selective 'reader' proteins of the YTH family, which incorporate m6A-modified mRNAs into pathways of RNA metabolism. Here, we show that the m6A-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells. Knockdown of YTHDC1 results in an extended residence time for nuclear m6A-containing mRNA, with an accumulation of transcripts in the nucleus and accompanying depletion within the cytoplasm. YTHDC1 interacts with the splicing factor and nuclear export adaptor protein SRSF3, and facilitates RNA binding to both SRSF3 and NXF1. This role for YTHDC1 expands the potential utility of chemical modification of mRNA, and supports an emerging paradigm of m6A as a distinct biochemical entity for selective processing and metabolism of mammalian mRNAs.

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Intronless mRNAs transit through nuclear speckles to gain export competence.

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The export factor Yra1 modulates mRNA 3' end processing.

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Altered RNA processing and export lead to retention of mRNAs near transcription sites and nuclear pore complexes or within the nucleolus.

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Selective nuclear export of mRNAs is promoted by DRBD18 in Trypanosoma brucei.

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