Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs.
A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-β pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions.
Jima
Dereje D
DD
Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
Zhang
Jenny
J
Jacobs
Cassandra
C
Richards
Kristy L
KL
Dunphy
Cherie H
CH
Choi
William W L
WW
Au
Wing Yan
WY
Srivastava
Gopesh
G
Czader
Magdalena B
MB
Rizzieri
David A
DA
Lagoo
Anand S
AS
Lugar
Patricia L
PL
Mann
Karen P
KP
Flowers
Christopher R
CR
Bernal-Mizrachi
Leon
L
Naresh
Kikkeri N
KN
Evens
Andrew M
AM
Gordon
Leo I
LI
Luftig
Micah
M
Friedman
Daphne R
DR
Weinberg
J Brice
JB
Thompson
Michael A
MA
Gill
Javed I
JI
Liu
Qingquan
Q
How
Tam
T
Grubor
Vladimir
V
Gao
Yuan
Y
Patel
Amee
A
Wu
Han
H
Zhu
Jun
J
Blobe
Gerard C
GC
Lipsky
Peter E
PE
Chadburn
Amy
A
Dave
Sandeep S
SS
D001402:B-Lymphocytes; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling / Q000379:methods*; D015723:Gene Library; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
D035683:MicroRNAs