A low-complexity region in human XRN1 directly recruits deadenylation and 
decapping factors in 5'-3' messenger RNA decay

Chang, C-T; Muthukumar, S; Weber, R; Levdansky, Y; Chen, Y; Bhandari, D; Igreja, C; Wohlbold, L; Valkov, E; Izaurralde, E

doi:10.1093/nar/gkz633

アイテム詳細

登録内容を編集ファイル形式で保存

一時保存へ追加

タグ情報を表示リリース履歴を表示詳細要約

公開

学術論文

A low-complexity region in human XRN1 directly recruits deadenylation and decapping factors in 5'-3' messenger RNA decay

MPS-Authors

/persons/resource/persons272371

Chang, C-T
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons273098

Muthukumar, S
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons272040

Weber, R
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons272377

Levdansky, Y
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons271770

Chen, Y
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons273087

Bhandari, D
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons271538

Igreja, C
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;
Regulation and Post-Translational Modification of Gene Expression in Nematodes Group, Department Integrative Evolutionary Biology, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons273100

Wohlbold, L
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons272049

Valkov, E
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons271767

Izaurralde, E
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

External Resource

There are no locators available

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

フルテキスト (公開)

公開されているフルテキストはありません

付随資料 (公開)

There is no public supplementary material available

引用

Chang, C.-T., Muthukumar, S., Weber, R., Levdansky, Y., Chen, Y., Bhandari, D., Igreja, C., Wohlbold, L., Valkov, E., & Izaurralde, E. (2019). A low-complexity region in human XRN1 directly recruits deadenylation and decapping factors in 5'-3' messenger RNA decay. Nucleic Acids Research (London), 47(17), 9282-9295. doi:10.1093/nar/gkz633.

引用: https://hdl.handle.net/21.11116/0000-000A-6096-0

要旨

XRN1 is the major cytoplasmic exoribonuclease in eukaryotes, which degrades deadenylated and decapped mRNAs in the last step of the 5'-3' mRNA decay pathway. Metazoan XRN1 interacts with decapping factors coupling the final stages of decay. Here, we reveal a direct interaction between XRN1 and the CCR4-NOT deadenylase complex mediated by a low-complexity region in XRN1, which we term the 'C-terminal interacting region' or CIR. The CIR represses reporter mRNA deadenylation in human cells when overexpressed and inhibits CCR4-NOT and isolated CAF1 deadenylase activity in vitro. Through complementation studies in an XRN1-null cell line, we dissect the specific contributions of XRN1 domains and regions toward decay of an mRNA reporter. We observe that XRN1 binding to the decapping activator EDC4 counteracts the dominant negative effect of CIR overexpression on decay. Another decapping activator PatL1 directly interacts with CIR and alleviates the CIR-mediated inhibition of CCR4-NOT activity in vitro. Ribosome profiling revealed that XRN1 loss impacts not only on mRNA levels but also on the translational efficiency of many cellular transcripts likely as a consequence of incomplete decay. Our findings reveal an additional layer of direct interactions in a tightly integrated network of factors mediating deadenylation, decapping and 5'-3' exonucleolytic decay.