scholarly journals Correction: Trans-splicing of the C. elegans let-7 primary transcript developmentally regulates let-7 microRNA biogenesis and let-7 family microRNA activity (doi: 10.1242/dev.172031)

Development ◽  
2019 ◽  
Vol 146 (14) ◽  
pp. dev182212
Author(s):  
Charles Nelson ◽  
Victor Ambros
2018 ◽  
Author(s):  
Charles Nelson ◽  
Victor Ambros

SUMMARYlet-7 is a microRNA whose sequence and roles as a regulator of developmental progression are conserved throughout bilaterians. In most systems, transcription of the let-7 locus occurs relatively early in development, whilst processing of let-7 primary transcript into mature microRNA arises later and is associated with cellular differentiation. In C. elegans and other animals, the RNA binding protein LIN-28 post-transcriptionally inhibits let-7 biogenesis at early developmental stages. The mechanisms by which LIN-28 and other factors developmentally regulate let-7 biogenesis are not fully understood. Nor is it understood how the developmental regulation of let-7 might influence the expression or activities of other microRNAs of the same seed family. Here we show that in C. elegans, the primary let-7 transcript (pri-let-7) is trans-spliced to SL1 splice leader at a position downstream of the let-7 precursor stem-loop, producing a short, polyadenylated downstream mRNA. The trans-splicing event negatively impacts the biogenesis of mature let-7 microRNA in cis, likely by destabilizing the upstream pri-let-7 fragment. Moreover, the trans-spliced downstream mRNA contains complimentary sequences to multiple members of the let-7 seed family (let-7fam), and thereby serves as a sponge to negatively regulate let-7fam function in trans. Thus, this study provides evidence for a mechanism by which splicing of a microRNA primary transcript can negatively regulate said microRNA in cis as well as other microRNAs in trans.HIGHLIGHTSThe let-7 primary transcript is trans-spliced to produce an RNA that functions as a sponge that negatively regulates the let-7-family microRNAs.Trans-splicing of this RNA negatively impacts let-7 microRNA biogenesis.LIN-28 regulates this trans-splicing event


1990 ◽  
Vol 10 (4) ◽  
pp. 1764-1768
Author(s):  
R F Liou ◽  
T Blumenthal

The nematode Caenorhabditis elegans has an unusual small nuclear RNA, containing a 100-nucleotide RNA molecule, spliced leader RNA, which donates its 5' 22 nucleotides to a variety of recipient RNAs by a trans-splicing reaction. The spliced leader RNA has a 5' trimethylguanosine (TMG) cap, which becomes the 5' end of trans-spliced mRNAs. We found that mature trans-spliced mRNAs were immunoprecipitable with anti-TMG cap antibodies and that TMG-containing dinucleotides specifically competed with the trans-spliced mRNAs for antibody binding. We also found that these mRNAs retained their TMG caps throughout development and that the TMG-capped mRNAs were polysome associated. Since the large majority of C. elegans mRNAs are not trans-spliced, the addition of the spliced leader and its TMG cap to a limited group of recipient RNAs may create a functionally distinct subset of mRNAs.


RNA ◽  
2007 ◽  
Vol 13 (4) ◽  
pp. 511-520 ◽  
Author(s):  
M. MacMorris ◽  
M. Kumar ◽  
E. Lasda ◽  
A. Larsen ◽  
B. Kraemer ◽  
...  
Keyword(s):  

1990 ◽  
Vol 14 (2-3) ◽  
pp. 115-115 ◽  
Author(s):  
David Hirsh ◽  
X. -Y. Huang
Keyword(s):  

1988 ◽  
Vol 8 (6) ◽  
pp. 2597-2603
Author(s):  
S I Miller ◽  
D F Wirth

The 5' ends of Leishmania mRNAs contain an identical 35-nucleotide sequence termed the spliced leader (SL) or 5' mini-exon. The SL sequence is at the 5' end of an 85-nucleotide primary transcript that contains a consensus eucaryotic 5' intron-exon splice junction immediately 3' to the SL. The SL is added to protein-coding genes immediately 3' to a consensus eucaryotic 3' intron-exon splice junction. Our previous work demonstrated possible intermediates in discontinuous mRNA processing that contain the 50 nucleotides of the SL primary transcript 3' to the SL, the SL intron sequence (SLIS). These RNAs have a 5' terminus at the splice junction of the SL and the SLIS. We examined a Leishmania nuclear extract for these RNAs in ribonucleoprotein (RNP) particles. Density centrifugation analysis showed that the SL RNA is predominantly in RNP complexes at 60S, while the SLIS-containing RNAs are in complexes at 40S. We also demonstrated that the SLIS can be released from polyadenylated RNA by incubation with a HeLa cell extract containing debranching enzymatic activity. These data suggested that Leishmania enriettii mRNAs are assembled by bimolecular or trans splicing as has been recently demonstrated for Trypanosoma brucei. Furthermore, we determined the partial sequence of the Leishmania U2 equivalent RNA and demonstrated that it cosediments with the SL RNA at 60S in a nuclear extract. These RNP particles may be analogous to so-called spliceosomes that have been demonstrated in other systems.


RNA ◽  
2007 ◽  
Vol 13 (9) ◽  
pp. 1409-1426 ◽  
Author(s):  
J. H. Graber ◽  
J. Salisbury ◽  
L. N. Hutchins ◽  
T. Blumenthal

2020 ◽  
Vol 6 (50) ◽  
pp. eabc1450
Author(s):  
C. Cassart ◽  
C. Yague-Sanz ◽  
F. Bauer ◽  
P. Ponsard ◽  
F. X. Stubbe ◽  
...  

Serine 2 phosphorylation (S2P) within the CTD of RNA polymerase II is considered a Cdk9/Cdk12-dependent mark required for 3′-end processing. However, the relevance of CTD S2P in metazoan development is unknown. We show that cdk-12 lesions or a full-length CTD S2A substitution results in an identical phenotype in Caenorhabditis elegans. Embryogenesis occurs in the complete absence of S2P, but the hatched larvae arrest development, mimicking the diapause induced when hatching occurs in the absence of food. Genome-wide analyses indicate that when CTD S2P is inhibited, only a subset of growth-related genes is not properly expressed. These genes correspond to SL2 trans-spliced mRNAs located in position 2 and over within operons. We show that CDK-12 is required for maximal occupancy of cleavage stimulatory factor necessary for SL2 trans-splicing. We propose that CTD S2P functions as a gene-specific signaling mark ensuring the nutritional control of the C. elegans developmental program.


Sign in / Sign up

Export Citation Format

Share Document