4.7 Article

The Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is Essential for snoRNA Biogenesis in Trypanosoma brucei

Journal

JOURNAL OF MOLECULAR BIOLOGY
Volume 429, Issue 21, Pages 3301-3318

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2017.04.015

Keywords

Trypanosomes; poly (A) polymerase; canonical polyadenylation; non-coding RNAs; snoRNA maturation

Funding

  1. Israel-US Binational Science Foundation [2011254]
  2. I-core Program of the Planning and Budgeting Committee
  3. Israel Science Foundation [1796/12]
  4. David and Inez Myers Chair in RNA silencing of diseases
  5. Div Of Civil, Mechanical, & Manufact Inn
  6. Directorate For Engineering [2011254] Funding Source: National Science Foundation

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The parasite Trypanosome brucei is the causative agent of African sleeping sickness and is known for its unique RNA processing mechanisms that are common to all the kinetoplastidea including Leishmania and Trypanosome cruzi. Trypanosomes possess two canonical RNA poly (A) polymerases (PAPs) termed PAP1 and PAP2. PAP1 is encoded by one of the only two genes harboring cis-spliced introns in this organism, and its function is currently unknown. In trypanosomes, all mRNAs, and non-coding RNAs such as small nucleolar RNAs (snoRNAs) and long non-coding RNAs (IncRNAs), undergo trans-splicing and polyadenylation. Here, we show that the function of PAP1, which is located in the nucleus, is to polyadenylate non-coding RNAs, which undergo trans-splicing and polyadenylation. Major substrates of PAP1 are the snoRNAs and IncRNAs. Under the silencing of either PAP1 or PAP2, the level of snoRNAs is reduced. The dual polyadenylation of snoRNA intermediates is carried out by both PAP2 and PAP1 and requires the factors essential for the polyadenylation of mRNAs. The dual polyadenylation of the precursor snoRNAs by PAPs may function to recruit the machinery essential for snoRNA processing. (C) 2017 Elsevier Ltd. All rights reserved.

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