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We thank Y. Ma and L. Zhang (Chinese Academy of Medical Sciences,
Beijing) for helping generate knockout mice; K. Li in our lab for
technical assistance; L. Wang, M. Wen, D. Han, and J. Li in our lab for
helpful discussions; and Q. Li (GCBI and Genminix Informatics Co., Ltd.)
for bioinformatics assistance. The data presented in this paper are
tabulated in the main paper and in the supplementary materials. The
data presented in this paper are tabulated in the main paper and in
the supplementary materials and were deposited in the Gene Expression
Omnibus (GEO) data repository with the following accession
numbers: GSE102179 and GSE102218 (transcriptome microarray data),
GSE100873 (RNA-sequencing data), GSE100739 (ribosomal-profiling
data), and GSE100229 (modified cross-linked RIP sequencing data).
This work is supported by grants from the National Natural Science
Foundation of China (81788104, 31390431, 31470871, 81671566, and
31722019), CAMS Innovation Fund for Medical Sciences (2016-12M-1-
003), and Shanghai Rising-Star Program (16QA1404700). X.C. and
P. W. designed the experiments; P. W., J.X., and Y. W. performed the
experiments; X.C. and P. W. analyzed data and wrote the paper;
and X.C. was responsible for research supervision, coordination,
and strategy. The authors declare no competing financial interests.
Materials and Methods
Figs. S1 to S26
7 June 2017; accepted 13 October 2017
Published online 26 October 2017
Fig. 4. lncRNA-ACOD1 promotes GOT2 enzymatic activity and
functions through GOT2-catalyzed metabolites. (A) GOT2-binding
RNAs were analyzed by RNA sequencing of GOT2 antibody-retrieved
complexes. Data are shown as read density around lncRNA-ACOD1 loci
(upper) and lncRNA-ACOD1 RNA (lower). Red bar indicates the protein-binding site immune to ribonuclease I (RNase I) digestion. (B) Top:
lncRNA-ACOD1–retrieved GOT2 peptide identified by MS analysis and its
position in the GOT2 protein linear structure and spatial structure (Protein
Data Bank 3PDB) (highlighted in yellow). Bottom: GOT2 protein sequence
conservation in vertebrates. (C) QPCR detection of lncRNA-ACOD1 retrieved
by full-length or domain-truncated GOT2-FLAG using FLAG antibody in the
RIP assay with human embryonic kidney (HEK) 293Tcells transfected with
indicated vectors. BS, binding site; C-SD, C-terminal part of the small domain;
LD, large domain; N-arm, N-terminal arm; N-SD, N-terminal part of the small
domain; D, deletion. n = 3. (D) Michaelis-Menten plots for GOT2 enzymatic
reactions with oxaloacetic acid (OAA, 0 to 100 mM, n = 4) and L-glutamic
acid (L-Glu, 100 mM), in the presence of 10 nM RNA (lncRNA-ACOD1,
antisense control, or 5′ end–binding site mutant). [E], enzyme concentration.
(E) Targeted metabolomics detection of L-aspartate (L-Asp) and a-ketoglutarate
(a-KG) through LC-MS with liver tissues from lncRNA-ACOD1−/− and WT
mice 36 hours after intraperitoneal injection with VSV (1 × 106 PFU/g).
(F) Determination of VSV loads by TCID50 assay in organ homogenate
supernatants of lncRNA-ACOD1−/− mice intraperitoneally injected with
L-Asp (5 mg/g body weight) or a-KG (5 mg/g body weight) and, 2 hours later,
intraperitoneally injected with VSV (1 × 107 PFU/g) for 36 hours. n = 4.
*P < 0.05 and **P < 0.01 (two-tailed Student’s t test). (G) Survival of
7-week-old lncRNA-ACOD1−/− mice treated as in (F). n = 5. Log-rank
(Mantel-Cox) test, P < 0.01.